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Having muscle tissue in our bronchioles that can constrict seems like a poor choice for tissue. Why would our airway want to ever close up? Wouldn't it be more beneficial for our bronchioles to just remain open?
There are at least two things to consider.
First, ability to limit airflow is a defense mechanism for animal. Imagine getting into area of some sort of toxic evaporation, e.g. CO2 cloud near volcano , then it makes sense to decrease delivery of toxin via lungs to minimum. As I understand, that is what an allergic asthma attack. (Sorry for not providing good enough source of that)
Secondly, you are incorrect in assuming that normal state is "dilated". Dilation of branchioles is sympathetic ("fight-and-fly") response of the nervous system to something like danger, that requires short-term boost in energy production. That is, by default, your airflow is limited. Probably, to limit amount of energy you effectively burn via oxygenation. But most importantly, you leave yourself a reserve in terms of oxygen supply for critical moments.
Some more information you might find here.
Our airways close up to make them more efficient. The respiratory tree from the mouth to the terminal bronchioles can't absorb oxygen, so each time you breath all the air moved into and out of the trachae, bronchi and terminal bronchioles is extra unnecessary work for the muscles. We can make it more efficient by shrinking the size of those tubes down by contracting the smooth muscle.
When you exercise these small tubes won't be large enough to get enough air in and out, so the smooth muscle relaxes to allow more air to move into the lung faster. It's a bit less efficient, but necessary when you need a lot of oxygen.
Why is there smooth muscle in our bronchioles? - Biology
Skeletal muscle: Produces movement, maintains posture, stabilises joints and generates heat
Smooth muscle: Found in the walls of hollow organs
Cardiac muscle: Exists only in your heart
You've got around 650 muscles in your body, and they make up roughly half of your bodyweight. These muscles can be divided into three different groups: skeletal, smooth and cardiac. All of these muscles can stretch and contract, but they perform very different functions.
The tissue most commonly thought of as muscle is skeletal muscle. Skeletal muscles cover your skeleton, giving your body its shape. They are attached to your skeleton by strong, springy tendons or are directly connected to rough patches of bone. Skeletal muscles are under voluntary control, which means you consciously control what they do.
Just about all body movement, from walking to nodding your head, is caused by skeletal muscle contraction. Your skeletal muscles function almost continuously to maintain your posture, making one tiny adjustment after another to keep your body upright. Skeletal muscle is also important for holding your bones in the correct position and prevents your joints from dislocating. Some skeletal muscles in your face are directly attached to your skin. The slightest contraction of one of these muscles changes your facial expression.
Skeletal muscle generates heat as a by-product of muscle activity. This heat is vital for maintaining your normal body temperature.
Smooth muscle is found in the walls of hollow organs like your intestines and stomach. They work automatically without you being aware of them. Smooth muscles are involved in many 'housekeeping' functions of the body. The muscular walls of your intestines contract to push food through your body. Muscles in your bladder wall contract to expel urine from your body. Smooth muscles in a woman's uterus (or womb) help to push babies out of the body during childbirth. The pupillary sphincter muscle in your eye is a smooth muscle that shrinks the size of your pupil.
Your heart is made of cardiac muscle. This type of muscle only exists in your heart. Unlike other types of muscle, cardiac muscle never gets tired. It works automatically and constantly without ever pausing to rest. Cardiac muscle contracts to squeeze blood out of your heart, and relaxes to fill your heart with blood.
Airway Smooth Muscle and Asthma
Structure and Function of Airway Smooth Muscle
Airway smooth muscle is a structural component of the walls of all of the airways within the bronchial tree, from the trachea to the smallest respiratory bronchioles (1,2) . In the lung parenchymal tissue, smooth muscle is found within the alveolar ducts that form the entrance to alveolar sacs and may also be dispersed within other areas of the lung parenchyma. In the trachea, the smooth muscle is contained solely within the trachealis membrane that extends along the dorsal side of the trachea where the trachea abuts the esophagus (3) . The trachealis membrane, which contains a thin layer of muscle tissue adjacent to the mucosal membrane that lines the entire trachea, connects the ends of the horseshoe-shaped rings of cartilage that form the length of the trachea. In the largest bronchi, bundles of smooth muscle are arranged circumferentially and helically within the airway wall just below the mucosal membrane (4) , and are surrounded by rings of cartilage, which make these bronchi stiff and may limit narrowing of the lumen when the airway muscle contracts (1,5,6) . As the bronchi divide into successive generations within the lungs, the amount of cartilage diminishes and takes the form of irregular plates. In the more distal generations of intra-parenchymal bronchi (bronchioles), the cartilage entirely disappears from the airway wall, and the smooth muscle layer and associated connective tissue represents the major structural component of the wall (2) . Thus in these airways, airway circumference and stiffness is regulated primarily by the smooth muscle tissue. The constriction of the airway smooth muscle in the smaller bronchi and bronchioles can result in airway closure and obstruction of the airway lumen, completely blocking airflow, as occurs in asthma (7) .
Airway smooth muscle may be the only smooth muscle tissue in the body for which the normal physiologic function is unknown. Although a number of hypotheses have been advanced for the function of airway smooth muscle, there is considerable debate as to whether it has any beneficial function at all! As the contraction of airway smooth muscle results in airway narrowing and the obstruction of airflow, clearly widespread airway constriction is not beneficial to breathing or health. Indeed, pervasive airway narrowing and airway smooth muscle hyperresponsiveness is considered a cardinal pathophysiologic feature of asthma. The ablation of localized regions of airway smooth muscle through the application of heat is currently being applied as a treatment for asthma (8) , and the use of gene therapy to inactivate the contractile mechanism of airway smooth muscle has been proposed as a treatment for asthma (9) . The fact that the widespread constriction of airway smooth muscle has pathological consequences has led to the suggestion that airway smooth muscle may in fact be “the appendix of the lung” – in essence, a vestigial organ with no useful function (10) !
If airway smooth muscle does serve a useful function, what might that function be? The normal function of airway smooth muscle has been debated for decades, and a variety of possible functions have been proposed for it (11) . One physiologic function that has been traditionally ascribed to airway smooth muscle is that of modulating the distribution of ventilation to optimize ventilation perfusion matching. The contraction of the smooth muscle in the alveolar ducts and small airways can markedly influence the distensibility of the lungs thus changes in bronchomotor tone might influence ventilation distribution by locally modulating lung compliance, thus improving the homogeneity of lung expansion. An additional mechanism by which airway smooth muscle might regulate the ventilation distribution is through alterations in airway tone induced by changes in CO2. As CO2 causes the relaxation of airway smooth muscle (12) , inadequate ventilation of local lung units that results in a build-up of CO2 might lead to airway dilation and thus enhance the ventilation of the lung units that they subserve. Other functions have been proposed for airway smooth muscle, among them: that it protects the airways from overdistension or distortion during breathing (13) that it optimizes anatomic dead space volume (1,14) that it assists in mucous clearance by modulating the location and extent of airway compression during cough (11) that it assists in exhalation or mucous propulsion through peristalsis (15) that it stabilizes the large airways during cough (6) . Critics argue that while some of these arguments may be plausible, it is difficult to make a compelling argument for any of them based on the available experimental evidence (10,16) .
Recent advances in the study of airway smooth muscle have led to the recognition that it has complex physiologic properties beyond those of simply contracting and relaxing in response to external stimulation – these discoveries may enhance our perspectives on the normal function of the muscle (17–20) . The contractility of airway smooth muscle and its material properties are highly malleable and are modulated dynamically in response to forces that are imposed on it (18,19,21) . In the lung this may be a critical property, as the process of breathing results in an environment in which the physical forces imposed on the airways are constantly changing, and both airway caliber and stiffness need to be dynamically adjusted to accommodate to changes in lung volume and ventilatory patterns. Furthermore, airway smooth muscle is now widely accepted to be a synthetic organ, capable of producing and secreting immunomodulatory and other compounds in response to a variety of external stimuli (20) . Its phenotypic status is also dynamic – airway smooth muscle cells can actively transition between a contractile and a synthetic state in response to multiple cues from the local environment, such as mechanical stimuli and tissue matrix interactions (20,22) . Pathophysiologic conditions of the airways such as asthma result in alterations in all of these properties: asthma is associated with the increased hypersensitivity of the airways to contractile stimuli, alterations in its response to mechanical forces during breathing, and enhanced secretion of inflammatory mediators and the modulation of its structural properties. The degree to which alterations in these functions are interrelated and underlie the pathophysiologic features of asthma are the subjects of intensive investigation. No doubt, better understanding of the broad functional properties of airway smooth muscle may provide new insights into the role of airway smooth muscle in normal lung function.
Why is there smooth muscle in our bronchioles? - Biology
The respiratory system consists of two divisions with distinct structural elements that reflect their unique functions. These include:
- The conducting airways, which serve to conduct, clean, warm, and moisten the air. This portion is composed of the nose, pharynx, larynx, trachea, bronchi, and bronchioles.
- The respiratory airways, which facilitate gas exchange. These are located entirely within the lung and are represented by respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli.
The epithelium lining the respiratory tract from the nasal fossa through the bronchi is called the respiratory mucosa and is characterized by a pseudostratified ciliated epithelium with abundant non-ciliated cells known as goblet cells. In the lamina propria there are mixed seromucous (protein- and mucous-secreting) glands, lymphatic tissue, and broad veins.
The conducting airways are divided into two main sections:
- Extrapulmonary air conduits are located outside of the lungs and begin with the nose, pharynx and larynx. The trachea is continuous with the larynx above and the two primary bronchi below. It is the supporting framework for 16-20 C-shaped hyaline cartilages. These cartilage "bracelets" are open on the posterior wall of the trachea adjacent to the esophagus. A bundle of smooth muscle fibers bridges the gap between the two ends of the cartilage.
- Intrapulmonary air conduits extend from the intralobar bronchi to the terminal bronchioles. When the bronchi enter the lung, the C-shaped cartilages that characterize the trachea and primary bronchi are replaced by irregular plates or cartilage that completely surround the cylindrical muscular airway tube. Cartilage disappears in the terminal bronchioles, which have narrowed to a diameter of 1 millimeter. The terminal bronchioles initially have a ciliated columnar epithelium that soon transitions to a low cuboidal epithelium. Mucous and seromucous glands and diffuse lymphatic tissue are associated with smaller bronchi but are not found distal to the region where there is a loss of cartilage plates.
The respiratory airways extend from the respiratory bronchioles to the alveoli.
- The respiratory bronchioles have a diameter of 0.5 millimeters and feature a few alveoli scattered along their walls. The epithelium here remains low cuboidal. Each respiratory bronchiole branches into between 2 and 11 alveolar ducts that still contain smooth muscle fibers in their walls. Along these walls, the alveolar ducts give rise to single alveoli and to numerous alveolar sacs, which are associated with 2 to 4 alveoli. The space at the entrance from the alveolar duct to an alveolar sac is referred to as the atrium.
- Alveoli can be studied most easily in preparations of expanded lung, especially in those areas in which erythrocytes have been retained in the capillaries. Alveoli have a distinct cup shape separated by loop- or crescent-shaped walls known as interalveolar septa. The interalveolar septa contain myriad capillaries.
The interface between the capillary lumen and the alveolar epithelium is known as the air-blood barrier. The barrier consists of the endothelium of the capillary, the epithelium of the alveolus, and their shared basement membrane.
The surface epithelium of the alveoli contains two developmentally related but functionally distinct cells, known as pneumocytes. Type I pneumocytes are attenuated vesicle-studded cells that line the alveolar walls near the capillaries. Only their flattened nuclei can be recognized with certainty by light microscopy. Type II pneumocytes are cuboidal and occur singly or in small clusters between type I cells. They contain 0.2 to 1 micron wide multilamellar bodies that contain a high content of phospholipid that is the precursor to pulmonary surfactant, which interferes with the surface tension in the alveoli that would otherwise cause them to collapse. Club (Clara) cells are also thought to participate in the synthesis of surfactant. Type II cells serve as precursors to type I cells.
Where there are no capillaries, the alveolar septum contains fibroblasts, collagen, elastic fibers, smooth muscle cells, and macrophages known as dust cells. Also notable are alveolar pores, which equalize air pressure between the alveoli.
Circulatory System of the Lung
Branches of the pulmonary artery accompany the bronchi to the level of the respiratory bronchioles. From there they branch into an extensive network of capillaries suspended within the alveolar walls. Venules arising from these capillaries join in the intersegmental connective tissue and later empty into the pulmonary veins. Bronchi and connective tissue septa within the lung are vascularized by branches of the bronchial arteries, which are part of the systemic circulatory system. These two systems anastomose at the level of alveoli arising from the respiratory bronchioles.
Location and Structure
Located within the lungs, bronchioles are tubular structures around 1mm in diameter  , consisting of connective tissues and some smooth muscles that keep the tubes open. These further divide into smaller tubules, which in turn continue subdividing till they reach the alveoli. Most parts of the bronchioles are lined with ciliated pseudostratified columnar or cuboidal epithelial tissues containing goblet cells.
Also called preterminal bronchioles, each lobular bronchiole branches into multiple terminal bronchioles after passing into a pulmonary lobule  .
Smaller tubules of around 0.5mm diameter, with ciliated cuboidal epithelium (there are no goblet cells)  . As their name suggests, these are considered the last conducting structure of the human respiratory system, eventually terminating in respiratory bronchioles [6, 7]
Terminal Bronchiole Histology
The final division of bronchioles, these end in 2-11 alveolar ducts [7, 8] , surrounded by the proteins elastin and collagen, and smooth muscles, each leading into an alveolar sac. These sacs contain multiple alveoli, encircled by pulmonary system blood vessels  . Ciliated cuboidal epithelial cells line the respiratory bronchioles, while some non-ciliated cells, known as clara cells, are present as well  .
Any dust particles and germs present in the inhaled air stick to the mucus secreted by the goblet cells in the epithelium, so the cilia can ‘sweep’ it upward to be excreted through the oral or nasal cavity .
Function of Smooth Muscle
Like all muscle tissue, the function of smooth muscle is to contract. The image above shows how the actin and myosin fibers shorten, effectively shrinking the cell. However, there are some important differences in how the smooth muscle contracts, compared to other types of muscle. In skeletal muscle, a signal from the somatic nervous system traverses to the muscle, where it stimulates organelles in the muscle cell to release calcium. The calcium causes a protein to detach from actin, and myosin quickly binds to the opening on actin. Since there was always available ATP, the myosin uses it to quickly contract the cell.
The same is not true in smooth muscle tissue. In smooth muscle, the contraction is not controlled voluntarily by the somatic nervous system, but by signals from the autonomous nervous system, such as nerve impulses, hormones, and other chemicals released by specialized organs. Smooth muscle is specialized to contract persistently, unlike skeletal muscle which much contract and release quickly. Instead of a calcium trigger which sets off a contraction reaction, smooth muscle has more of a throttle, like in a car.
A nerve impulse or outside stimulus reaches the cell, which tells it to release calcium. Smooth muscle cells do not have a special protein on actin which prevents myosin from binding. Rather, actin and myosin are constantly binding. But, myosin can only hold on and crawl forward when given energy. Inside smooth muscle cells is a complex pathway which allows the level of calcium to control the amount of ATP available to myosin. Thus, when the stimulus is removed, the cells do not relax right away. Myosin continues to bind to actin and crawl along the filaments until the level of calcium falls.
Function of the Bronchioles
The bronchioles serve as a transition between the large cartilage supported bronchi that enter the lungs and the tiny alveolar ducts that connect directly to the alveoli. The bronchioles carry oxygen rich air into the lungs and carry carbon dioxide rich air out of the lungs, thereby aiding in the processes of breathing and respiration. The smooth muscle that surround the bronchioles can constrict or dilate the airway, which can aid in getting the proper amount of oxygen into the blood.
Materials and Methods
Tissue preparation and apparatus of measurement
The apparatus and tissue preparation have been described previously (Herrera et al., 2002 Herrera et al., 2004). Porcine tracheal smooth muscle (trachealis) was used for the experiments. The tracheas were obtained from a local abattoir. The parallel in situ arrangement of trachealis cells in a bundle and low resting tension made the preparation ideal for this study. After removal from the animals, the tracheas were placed in physiological saline solution (PSS) at 4°C. In situ length (Lin situ) of a trachealis strip from one cartilage attachment to the other was measured before the C-shaped cartilage was cut. Attention was paid to the appearance of the epithelial-mucosal layer of the intact trachea: a wrinkled epithelial-mucosal layer usually indicates contracted smooth muscle cells underneath. Any such trachea was discarded because the in situ length could not be accurately measured. A rectangular sheet of relaxed smooth muscle tissue at its in situ length, free of connective tissue, was dissected from the trachea. The piece of tissue was then cut into multiple strips along the longitudinal axes of the cell bundles all the strips used in a single experiment had the same initial length as a result. The muscle preparations were ∼11×1×0.3 mm in dimension. The strips of muscle were attached to aluminum foil clips at both ends and mounted in a muscle bath. One end of the strip was connected to a stationary hook and the other end to a length/force transducer (lever system) with a noise level of <0.1 mN and a compliance of ∼1 μm/mN (QJin Design, Winnipeg, Canada). The computer-controlled lever system was able to measure muscle force either at a constant length (isometric force), or allow the muscle to shorten under a constant load (isotonic contraction), or apply a step change in length to the muscle at any predetermined time. A step change in length was completed in less than 100 milliseconds.
Before a trachealis preparation was ready for experiment, it was equilibrated for about 1 hour at a predetermined length (0.75, 1.0 or 1.5 Lin situ). During the equilibration period, the muscle was electrically stimulated periodically to produce 12-second tetani at 5-minute intervals. The preparation was considered equilibrated when it developed a stable maximal isometric tetanic force with negligible resting tension. Isotonic shortenings were all initiated in an isometric state, i.e. the muscle was stimulated isometrically and only when the developed active force reached the level of a preset isotonic load was the muscle allowed to shorten isotonically. During relaxation, the muscle was not allowed to lengthen beyond the preset isometric length. Stimulation of the muscle was provided electrically with a 60 Hz alternating current at a voltage (20 V) that elicited maximal response from the muscle preparations. The onset and duration of the stimulation were computer-controlled. The muscle bath contained PSS with pH 7.4 at 37°C and aerated with a gas mixture containing 5% CO2/95% O2. The PSS had a composition of 118 mM NaCl, 4.5 mM KCl, 1.2 mM NaH2PO4, 22.5 mM NaHCO3, 2 mM MgSO4, 2 mM CaCl2 and 2 g/l dextrose.
Determination of the relationship between actively shortened muscle length and the associated active force
In an isotonic contraction (i.e. a contraction under constant load), a muscle will shorten dynamically until the system comes to a static mechanical equilibrium. Shortening stops when the static force generation of the muscle equals that of the applied load. This static force equilibrium occurs at the plateau of an isotonic contraction where the shortening velocity is zero. By applying different isotonic loads to the muscle, the corresponding shortened lengths (at plateaus) can be measured. In this study, a series of isotonic loads ranging from 10-90% of maximal isometric force (Fmax) were applied to a muscle to obtain the corresponding maximally shortened lengths, and thus obtaining the length-force relationship for the muscle preparation.
In experiments where a quick stretch was applied to the muscle followed by an isotonic contraction, the quick length change was accomplished by the rotation of the servo lever to which the muscle was attached, using the step-length-change feature of the apparatus. The change in length occurred 10 seconds before stimulation of the muscle to allow the passive viscoelastic tissue response to settle. The maximal isometric force (Fmax) obtained from a contraction immediately following a quick stretch was slightly lower than the Fmax obtained without a quick stretch. For each preparation, the Fmax post stretch was determined, and in the subsequent isotonic contraction, the isotonic load was calculated according to the post-stretch Fmax.
Analysis of force-velocity and force-power relationships
In our experiments, the maximal rate of shortening occurred near the beginning of an isotonic contraction. For each isotonic load, we measured the maximal rate of shortening, and the pair of data constituted a force-velocity point. Five such points were obtained at isotonic loads that were 10, 30, 50, 70 and 90% of Fmax. Because shortening velocity of smooth muscle is a function of both load and time (Dillon et al., 1981 Seow and Stephens, 1986), the force-velocity curve obtained with the present method did not represent the standard (or conventional) force-velocity relationship of the muscle owing to the fact that the velocities were measured at different times after stimulation. The reason that the velocities were measured at different times in the present study was because the onset of isotonic contraction was load-dependent, i.e. the greater the load, the later the onset. In this study, we were not interested in obtaining the standard force-velocity relationship of the muscle we were interested in comparing the velocities of the same muscle adapted to different lengths.
Determination of the relationship between isotonic load and the amount of shortening in a muscle adapted to different lengths
In this group of experiments, we determined the length-force relationship of trachealis preparations that were equilibrated for about 1 hour at one of the two lengths: 1.5 times the in situ length (Lin situ), and 0.75 Lin situ. Six muscle preparations from six pigs were used for this group of experiments. Three of the muscle preparations were equilibrated at 0.75 Lin situ the other three at 1.5 Lin situ. Five isotonic loads (as mentioned above) were used to generate a curve that described the relationship between the isotonic load and the corresponding maximal amount of shortening. At lighter loads (<50% Fmax) maximal shortening was reached in less than 12 seconds of stimulation at heavier loads, longer stimulation time (up to 27 seconds) was needed to obtain maximal shortening. It should be pointed out that the true plateau of an isotonic contraction may not be obtainable if there is ongoing adaptation of the muscle to length change. The protocol described above therefore excluded the effects of slow length adaptation that might occur in a prolonged contraction. For muscle preparations equilibrated at 1.5 Lin situ, the length-force relationship was first obtained with the muscle shortening (against the five isotonic loads, randomly applied) from the initial length of 1.5 Lin situ. The same preparations were then readapted at 0.75 Lin situ until their isometric force reached a stable, maximal level. This process (called length adaptation) took about 30-40 minutes and consisted of six to eight isometric contractions (12-second tetani) elicited at 5-minute intervals. The length-force relationship was then obtained with the muscle shortening from 0.75 Lin situ against five isotonic loads (10-90% Fmax as before, the Fmax however was that obtained at 0.75 Lin situ). In between isotonic contractions, at least one isometric contraction was elicited to determine the level of isometric force. Shortening at low isotonic loads often resulted in a reduction in the isometric force of the subsequent isometric contraction. Several isometric tetani (at 5-minute intervals) were often required to bring the isometric force back to the initial level before the isotonic contraction was elicited. For the muscle preparations equilibrated at 0.75 Lin situ, the length-force relationships were obtained in the reversed order as that described for the preparations equilibrated at 1.5 Lin situ. That is, a length-force relationship was obtained first at 0.75 Lin situ, followed by readapting the same muscle preparation at 1.5 Lin situ and then obtaining the length-force relationship for that length. Results from the two groups were not statistically different and were combined in the final analysis.
Electron microscopy (EM)
Muscle preparations were fixed for EM using a conventional protocol described previously (Herrera et al., 2002 Qi et al., 2002). Briefly, muscle preparations were fixed with the primary fixing solution (see below for details) for 15 minutes while they were still attached to the experiment apparatus. Care was taken not to physically perturb the tissue during the initial fixation. The tissue was then removed from the apparatus and cut into small cubes and immersed in the primary fixing solution for an additional 2 hours at 4°C. The primary fixing solution contained 2% glutaraldehyde, 2% paraformaldehyde and 2% tannic acid in 0.1 M sodium cacodylate buffer. In the process of secondary fixation, the small tissue cubes were put in 1% OsO4 in 0.1 M sodium cacodylate buffer for 2 hours. The tissue was then stained with 1% uranyl acetate, dehydrated with increasing concentrations of ethanol and embedded in resin (TAAB 812 mix). The resin blocks were sectioned with a diamond knife to obtain sections of ∼90 nm of thickness. The sections (on copper grids) were further stained with 1% uranyl acetate and Reynolds lead citrate. Images of thin sections of smooth muscle cells were obtain using a Phillips 300 electron microscope.
Morphometric and statistical analysis
Sampling and analysis were carried out `blind'. The codes indicating experimental conditions were revealed only after the analysis of each group was finished. Specialized image analysis software (Image Pro-Plus 3.0) was used to help with the manual counting of the thick filaments by marking and keeping track of the number of filaments counted (tag-point counting). The software also helped in determining distance between two points and area measurements.
Statistical analysis and comparison among data groups were performed by one-way ANOVA or Student's t-test. For morphometric measurements, data from each animal were averaged first before the means from different animals were averaged. Values were expressed as mean±s.e.m. The level of statistical significance was set at P<0.05.
Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis
Although susceptibility to cardiovascular disease (CVD) is different for every patient, why some patients with type 2 diabetes mellitus (T2DM) develop CVD while others are protected has not yet been clarified. Using T2DM-patient-derived human induced pluripotent stem cells (hiPSCs), we found that in patients protected from CVD, there was significantly elevated expression of an esterase, arylacetamide deacetylase (AADAC), in vascular smooth muscle cells (VSMCs). We overexpressed this esterase in human primary VSMCs and VSMCs differentiated from hiPSCs and observed that the number of lipid droplets was significantly diminished. Further metabolomic analyses revealed a marked reduction in storage lipids and an increase in membrane phospholipids, suggesting changes in the Kennedy pathway of lipid bioassembly. Cell migration and proliferation were also significantly decreased in AADAC-overexpressing VSMCs. Moreover, apolipoprotein E (Apoe)-knockout mice overexpressing VSMC-specific Aadac showed amelioration of atherosclerotic lesions. Our findings suggest that higher AADAC expression in VSMCs protects T2DM patients from CVD.
Keywords: cardiovascular disease, diabetes, induced pluripotent stem cell, disease modeling, lipid metabolism, cholesterol, Kennedy pathway, arylacetamide deacetylase, vascular smooth muscle cell, endothelial cell.
Between species the diameter of the bronchi and bronchioles vary greatly and more significantly than the variations of the trachea. The number of bronchial divisions before bronchioles are present varies by species - small mammals such as mice may have only 4/5 generations, whereas 12+ may be necessary in larger animals. Avian respiration is very different to that of mammals. The respiratory systems of non-homeotherms are also very different to that of mammals.
Each lung has a primary Bronchi, the left, and right Bronchus. These give rise to the secondary bronchi., which in turn gives rise to the tertiary bronchi. The tertiary bronchi divide into bronchioles. These are different from the tertiary bronchi, where their walls do not have hyaline cartilage ( a cartilage that is transparent) and have club cells ( dome-shaped cells found in the bronchioles of the lungs) in their epithelial lining. The epithelium changes from a simple ciliated columnar epithelium to a simple ciliated cuboidal epithelium , as the bronchioles keep decreasing in size. These bronchioles rely on elastic fibers, instead of a hyaline cartilage in order to maintain their patency. The inner lining of the bronchioles is thin, and has no gland, being surrounded by a smooth muscle. The bronchioles keep getting smaller as they divide into terminal bronchioles, marking the end of the conducting zone. Alveoli become present only when the conducting zone changes into the respiratory zone.
The terminal Bronchiole is the farthest segment of the conducting zone, branching off the lesser bronchioles. Both the terminal bronchiole divide to form the respiratory bronchioles, containing a small number of alveoli. These bronchioles contain a limited amount of ciliated cells and no goblet cells.
The respiratory bronchioles are the narrowest passageways of the lungs, a fifteenth of an inch breadth. The bronchus divides several times before they evolve into the bronchioles. These bronchioles deliver air to the surface of the lungs. The alveolar ducts are the farthest continuations of the respiratory bronchioles.
Bronchoconstriction, narrowing of the bronchioles may occur due to inhalation of toxic fumes, allergic agents, cold air and other irritants. By this, the body keeps the irritants in check. On the other hand, Bronchodilation is the process of the widening of the bronchioles. Adrenaline (the hormone that is released to counter stress) serves to dilate these passageways.