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Vascular Smooth Muscle


Introduction of smooth muscle

Smooth muscle is distributed in the visceral and vascular walls, so it is also called visceral muscle. The smooth muscle fibers are long fusiform and have no transverse stripes. It is innervated by autonomic nerves and is an involuntary muscle. This muscle contraction is slow and long lasting. The nucleus is a long elliptical or rod-shaped, located in the center. When contracted, the nucleus can be twisted and spiraled, and the sarcoplasm at both ends of the nucleus is rich. Smooth muscle fibers vary in size, generally 200 μm long and 8 μm in diameter; small vessel wall smooth muscle is as short as 20 μm, while pregnant uterine smooth muscle can be as long as 500 μm. Smooth muscle is mainly distributed in the walls of blood vessels, trachea, stomach, intestines and the like. Smooth muscle fibers can exist alone, most of which are bundled or layered. Unlike striated muscles, which are motility muscles, smooth muscles are primarily adapted to function as tonic muscles. The function of passive stretch and active shortening is significantly greater than striated muscles and often show automatic excitability. The smooth muscles of vertebrates are generally dominated by the dual inner nerve of the vegetative nervous system, and their nerve endings form a neural network between muscle cells, sometimes also with ganglion cells. Regarding the principle of contraction of smooth muscle, it is currently believed that it is contracted by the principle of "sliding filament theory" like striated muscle. Since each contraction unit is composed of thick myofilament (myosin) and thin myofilament (actin), one end of which is attached to the inner surface of the sarcolemma by thin filaments, and these attachment points are spiral. The myofilament unit is roughly parallel to the long axis of the smooth muscle, but has a certain inclination. The thick muscle wire has no M line, and half of the cross bridge on the surface oscillates in the opposite direction. Therefore, when the muscle fiber contracts, not only the thin muscle wire slides along the entire length of the thick muscle wire, but also the sliding direction of the adjacent thin muscle wire is relatively. Therefore, when the smooth muscle fibers contract, the overlapping range of the thick and thin muscle fibers is large, and the fibers are spirally twisted to become shorter and thicker.

In the blood vessel wall, it is divided into three layers of inner, middle and outer from the lumen to outward. The inner layer is covered by single-layer vascular endothelial cells (VECs) and supported by the basement membrane under VECs; the middle layer is mainly composed of vascular smooth muscle cells (VSMCs), the thickness and composition of which vary with vascular types; the outer layer consists of loose connective tissue. VECs have a selective barrier function, have anticoagulant and procoagulant effects and participate in the regulation of vascular motility, interact with platelets and white blood cells, and participate in inflammation. In addition, VECs also synthesizes and secretes a variety of connective tissue components, is an important factor in determining vascular activity and conformation. VSMCs in the middle layer of blood vessels are one of the important cells regulating blood pressure, and play an important role in the formation of various vascular diseases such as atherosclerosis (As), vascular restenosis and hypertension. When dysfunction of arterial endothelial leads to the disorder of expression and activation of various cytokines and vasoactive substances, the function and structure of VSMCs are changed, thereby promoting the formation and development of cardiovascular diseases.

Vascular Smooth Muscle

The features of vascular smooth muscle

VSMC is divided into two types: synthetic and contractile. The contracted VSMC is spindle-shaped, and its cytoplasm is filled with a large amount of actin and myosin, and the rough endoplasmic reticulum and Golgi are less, and are in a differentiated state. Synthetic VSMC is elliptical or spindle-shaped. The cytoplasm is rich in rough endoplasmic reticulum and Golgi complex. It can express various matrix proteins such as growth factors, cytokines and osteopontin (OPN), and produce and secrete, and large amount of collagen and extracellular matrix. Synthetic VSMC can migrate and proliferate, and they are in a dedifferentiated state. During the normal development of the body, the VSMC phenotype is transformed: mesenchymal cells with pluripotent differentiation ability, synthetic phenotypic smooth muscle cells and contractile phenotypic smooth muscle cells. The latter is a resting cell that mainly performs contractile function and has a weaker function of synthesizing extracellular matrix. However, under pathological conditions, the phenotype changes of VSMC are more complicated: (1) the contractile phenotype is transformed into a synthetic phenotype, and the synthesis and secretion functions are reactivated; (2) the DNA synthesis increases in the contractile cells, but the cells do not divide and proliferate, so after the cells appear hypertrophy, they still have a contractile phenotype. According to the theory of cell dynamics, the cells have undergone S phase DNA synthesis, but they are inhibited in G2. If appropriate stimulation is given in vitro culture, these cells can be converted into a synthetic type; (3) cells with multi-directional differentiation latent in the mature body are abnormally stimulated, these cells can be converted into a synthetic VSMC with strong synthetic secretion function.

The phenotype of VSMC cells has a variable nature. Under the action of various cytokines and growth factors, it can be transformed from a differentiated type with contractile function to a dedifferentiated type with migration and proliferation function. The transformation of this phenotype and the pathological process of cardiovascular disease have a close relationship. For example, the reversal of this phenotype is of great significance for the prevention and treatment of cardiovascular diseases. The normal mature blood vessel wall VSMC is contractile and in a differentiated state, belonging to differentiated VSMC, and synthesizes less OPN and matrix proteins. In the pathological state of hypertension, atherosclerosis and vascular restenosis, or VSMC is cultured in vitro, VSMC rapidly undergoes phenotypic transformation, becoming a dedifferentiated VSMC with weaker contractility and stronger synthesis ability. These cells can synthesize large amount of OPN and matrix proteins. In vitro differentiated VSMC, VSMC can be transformed from synthetic VSMC into differentiated VSMC with contractile function in serum-free starvation culture, which is a phenotypic reversal.

Clinical significance

In hypertension patient, aortic smooth muscle cells appear polyploid hypertrophy, and smooth muscle cells show phenotypic of conversion hyperplasia. At this time, arterial smooth muscle cells transform into synthetic smooth muscle cells, which migrate to the inner membrane and proliferation. As the cells are transformed into a synthetic form, their synthesis and secretion functions are abnormally enhanced, the collagen content of the membrane in the arteries is increased, the proportion of type I collagen is increased, and the compliance of blood vessels is decreased. In vitro experiments showed that VSMC, which is converted into a synthetic phenotype, secretes growth-promoting substances, such as platelet-derived growth factor and smooth muscle cell-derived growth factor, to promote VSMC proliferation in an autocrine or paracrine form. VSMC proliferation, hypertrophy, and increased secretion of extracellular matrix promote to thicken of the blood vessel wall, reduce the diameter of vascular and vascular compliance. These processes will extend the resistance vessels, and result in increased peripheral resistance, all of which constitute an important structural basis for elevated blood pressure. Therefore, it will be an effective treatment for hypertension by inhibiting VSMC hyperproliferation.

References:

  1. William T, Gerthoffer S.Mechanisms of vascular smooth muscle cell migration. Circ Res. 2007,100: 607-621.
  2. David M, et al.Notch and vascular smooth muscle cell phenotype. Circ Res. 2008, 103: 1370-1382.
  3. Shang Y, et al. Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation. J. Cell Biol. 2008, 181: 461-473.
  4. Johns DG, et al.Impaired ceramide signaling in spontaneously hypertension rat vascular smooth muscle:a possible mechanism for augmented cell proliferation. J Hypertens Suppl. 2001. 19: 63-70.
  5. Francis G. Myocardial matrix remodeling and the matrix metalloproteinases:influence on cardiac form and function. Physiol Rev. 2007, 87: 1285-1342.

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