Smooth muscle cell

Long-lasting vasoconstriction is produced by the ETs in almost all arteries and veins and several studies have shown that ET-1 causes a reduction in renal blood flow and urinary sodium excretion. ET-1 has been reported to be a potent mitogen in fibroblasts and aortic smooth muscle cells and to cause contraction of rat stomach strips, rat colon and guinea pig ileum. In the central nervous system, ETs have been shown to modulate neurotransmitter release. 

The myocytes of smooth muscle are approximately 100 to 500 p,m in length and only 2 to 6 p,m in diameter. Smooth muscle contains very few t-tubules and much less SR than skeletal muscle. The Ca that stimulates contraction in smooth muscle cells is predominantly extracellular in origin. This Ca enters the cell through Ca channels in the sarcolemmal membrane that can be opened by electrical stimulation, or by the binding of hormones or drugs. The contraction response time of smooth muscle cells is very slow compared with that of skeletal and cardiac muscle. 

In the vasculature, ANG H not only increases contraction of smooth muscle cells, but is also able to induce vascular injury. This can be prevented by blocking NFkB activation [3] suggesting a link between ANG II and inflammation processes involved in the pathogenesis of arteriosclerosis (see below). Thus, ACE inhibitors not only decrease vascular tone but probably also exert vasoprotective effects. 

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

Human umbilical vein endothelial cells (HUVEC) express the isoforms ECE-la, -lb, -Id and ECE-2. In these cells, ET-1 is secreted via both a constitutive and a regulated pathway. The ratio of released ET-1 big-ET-1 is 4 1. About 80% of the ET-1 is secreted at the abluminal cell surface of endothelial cells. ECE-isoforms are abundantly expressed on the cell surface of endothelial cells and to a lower level also on vascular smooth muscle cells. In atherosclerotic lesions of vessels, however, ECE expression in smooth muscle cells is upregulated. ECE isoforms expressed in smooth muscle cells contribute significantly to the generation of mature ET in normal and in particular atherosclerotic vessels. 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

Sites of endothelin-receptor expression. ETA receptors are expressed in the smooth muscle cells of the vascular medial layer and the airways, in cardiac myocytes, lung parenchyma, bronchiolar epithelial cells and prostate epithelial cells. ETB receptors are expressed in endothelial cells, in bronchiolar smooth muscle cells, vascular smooth muscle cells of certain vessels (e.g. saphenous vein, internal mammary artety), in the renal proximal and distal tubule, the renal collecting duct and in the cells of the atrioventricular conducting system. 

In addition, ETB receptors are upregulated in vessels with atherosclerotic lesions and in pulmonary vessels of patients with severe pulmonary hypertension. The upregulation can be attributed to increased ETB receptor expression in smooth muscle cells and to ETB receptors expressed on infiltrating macrophages. 

In the vascular system, endothelial ETB receptors mediate a transient vasodilation, whereas ETA receptors cause a long-lasting vasoconstriction. The role of ETb receptors expressed on smooth muscle cells... 

Cells in the atheroma derived from both macrophages and smooth muscle cells that have accumulated modified low-density lipoproteins. Their cytoplasm laden with lipid causes the foamy appearance on microscopy... 

G-actin (globular actin) has a molecular weight of about 42 kDa. In higher vertebrates, six isoforms of G-actin, which contain 374/375 residues, are expressed in a cell-specific manner. They are present in striated muscle cells (skeletal and cardiac isoforms), smooth muscle cells (vascular and visceral isoforms) and in non-muscle cells (two isoforms). 

Glucocorticoids. Figure 2 Cellular effect of glucocorticoids. Glucocorticoids can affect the activation of most resident and infiltrating cells with the airway suppressing either cell number or mediator release or both. In addition, glucocorticoids are able to decrease vascular permeablility (leak) within the airways that causes oedema and increase the expression of (32-receptors in smooth muscle cells. 

PDGF Isoforms consist of homo- and heterodimers of A- and B-polypeptide chains and homodimers of C- and D-polypeptide chains PDGFR Consists of PDGFR a and (3 receptors Embryonic development, particularly in the formation of the kidney, blood vessels, and various mesenchymal tissues. Proliferation of connective tissues, glial and smooth muscle cells... 

Induced by bacterial lipopolysaccharides or immune cytokines in macrophages, smooth muscle cells, and glia cells. Ca2+ is not required for the enzyme activation. 

The innermost layer of an artery, which consists of loose connective tissue covered by a monolayer of endothelium that resides on a basement membrane. In human arteries, the intima often contains resident smooth muscle cells even early in life. Atherosclerotic plaques form in the intima. 

Expression (Human) Tissues Leukocytes, thymus, spleen, liver, ovary Cells PBLs, neutrophils,T-cells, dendritic cells, mast cells, eosinophils, macrophages, leukocytes Tissues spleen, small intestine, placenta, lung smooth muscle, Cells bronchial smooth muscle, CD34+ hemapoietic progenitor cells, monocytes, macrophages, mast cells, eosinophils, neutrophils, PBLs, human umbilical vein endothelial cells Tissues, heart, skeletal muscle, spleen, brain, lymp node, adrenal medulla, lung, human pumonary/ saphenous vein Cells monocytes, macrophages, mast cells, eosinophils, cardiac muscle, coronary artery, PBLs... 

S1P2 Ubiquitous Gj/O. Gq, G12/13 Migration, vascular development, differentiation of vascular smooth muscle cells... 

In some cell types, e.g. in vascular smooth muscle cells, NPY appears to enhance cell growth. 

---