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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates synchronized contraction of the cardiac chambers, and contributing to co-ordination of function between cells of the arterial wall. Altered gap junctional coupling is implicated in the genesis of arrhythmia, a major cause of death in heart disease. Two abnormalities in myocardial gap junctions distribution at the border zone of infarcts and reduced levels of connexin43 (Cx43; alpha 1)--may lead to heterogeneous wavefront propagation and lowered conduction velocity, key factors that precipitate arrhythmia. In the major arteries, endothelial cells express Cx40 (alpha 5) and Cx37 (alpha 4) and, in some instances, also Cx43, whereas underlying medial smooth muscle cells express only Cx43. Increased Cx43 expression between medial smooth muscle cells is intimately linked to phenotypic transformation to the synthetic state in both early human coronary phenotypic transformation to the synthetic state in both early human coronary atherosclerosis, and in the response of the arterial wall to injury. The accumulating evidence suggests that gap junctions in both their guises--as pathways for cell-to-cell signalling in the vessel wall and as pathways for impulse conduction in the heart--may have key roles in the initial pathogenesis and eventual clinical manifestation of human cardiovascular disease.
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PMID:Cardiovascular disease. 1020 5

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates synchronized contraction of the cardiac chambers, and contributing to co-ordination of activities between cells of the arterial wall. In common with other multicellular systems, cardiovascular tissues express multiple connexin isotypes that confer distinctive channel properties. This review highlights how state-of-the-art immunocytochemical and cellular imaging techniques, as part of a multidisciplinary approach in gap junction research, have advanced our understanding of connexin diversity in cardiovascular cell function in health and disease. In the heart, spatially defined patterns of expression of three connexin isotypes-connexin43, connexin40, and connexin45-underlie the precisely orchestrated patterns of current flow governing the normal cardiac rhythm. Derangement of gap junction organization and/or reduced expression of connexin43 are associated with arrhythmic tendency in the diseased human ventricle, and high levels of connexin40 in the atrium are associated with increased risk of developing atrial fibrillation after coronary by-pass surgery. In the major arteries, endothelial gap junctions may simultaneously express three connexin isotypes, connexin40, connexin37, and connexin43; underlying medial smooth muscle, by contrast, predominantly expresses connexin43, with connexin45 additionally expressed at restricted sites. In normal arterial smooth muscle, the abundance of connexin43 gap junctions varies according to vascular site, and shows an inverse relationship with desmin expression and positive correlation with the quantity of extracellular matrix. Increased connexin43 expression between smooth muscle cells is closely linked to phenotypic transformation in early human coronary atherosclerosis and in the response of the arterial wall to injury. Current evidence thus suggests that gap junctions in both their guises, as pathways for cell-to-cell signaling in the vessel wall and as pathways for impulse conduction in the heart, contribute to the initial pathogenesis and eventual clinical manifestation of human cardiovascular disease.
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PMID:Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system. 1118 Jun 22

Paracrine cell-to-cell interactions are crucial events during atherogenesis. However, little is known about the role of direct intercellular communication via gap junctions during this process. We have investigated the expression pattern of 3 vascular gap junction proteins (connexins) in mouse and human atherosclerotic plaques. Low density lipoprotein receptor-deficient mice were fed a high-fat diet for 0, 6, 10, or 14 weeks to induce different stages of atherosclerosis. Connexin37 (Cx37) and Cx40 were detected in the endothelium, and Cx43 was detected in the media of nondiseased aortas. In early atheromas, endothelial and medial connexin expression remained unchanged, and "islets" of Cx43 in smooth muscle cells and Cx37 in macrophages were observed in the neointima. In advanced atheromas, Cx37 was detected in medial smooth muscle cells and in macrophages in the lipid core but not in the endothelium covering the plaques. Cx40 could also no longer be detected in the endothelium covering the plaques. Cx43, on the other hand, was detected in the endothelium covering the shoulder of the plaques and also sparsely in neointimal smooth muscle cells. Similar results were obtained for human carotid arteries. In conclusion, vascular connexins are differentially expressed by atheroma-associated cells within lesions. These observations suggest a role for gap junctional intercellular communication during atherogenesis.
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PMID:Altered pattern of vascular connexin expression in atherosclerotic plaques. 1183 20

Hyperhomocysteinemia (HHcy) is associated with impaired endothelial-dependent vasodilatation and increased risk of atherosclerosis and thrombosis. Here, we summarize some of our previous work on the effect of HHcy on pathways involved in endothelium-dependent vasodilatation, and present new data concerning the endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation. We showed that the 894 G>T single-nucleotide polymorphism in the human endothelial nitric oxide synthase gene (eNOS) increased the risk of recurrent venous thrombosis in individuals with elevated homocysteine levels, indicating that the pathophysiological mechanism in HHcy involves impaired NO-mediated vasodilatation. In addition, the EDHF-mediated vasodilatation of the renal artery was disturbed in diet-induced hyperhomocysteinemic rats. Interestingly, we demonstrated that pretreatment of rats with periodate-oxidized adenosine (Adox), which is an inhibitor of S-adenosylhomocysteine hydrolase, prevented the methionine-induced rise in plasma total Hcy (tHcy) levels but not the inhibition of the EDHF pathway. Furthermore, we demonstrated that S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet) levels were increased in the kidneys of diet-induced HHcy rats, resulting in a decreased AdoMet:AdoHcy ratio. In addition, we demonstrated that mRNA expression of Connexin 40, which is one of the structural subunits of gap-junctions, was down-regulated in endothelial cells of HHcy rats, and correlated with elevated AdoHcy levels in kidney of these rats. These finding suggest a key role for AdoHcy in relation to decreased Cx40 mRNA expression and impaired EDHF-mediated vasodilatation of HHcy rats.
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PMID:The role of hyperhomocysteinemia in nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation. 1570 55

Endothelial connexins have been linked to atherosclerosis and hypertension; however, little is know about their sensitivity to stimuli and individual functions. This study investigates the responses of endothelial connexin 37, connexin 40, and connexin 43 (Cx37, Cx40, and Cx43) to shear stress and substrate. Human endothelial cells were seeded on adsorbed collagen or a collagen gel containing smooth muscle cells and exposed to static or laminar shear stress. Connexin mRNA, protein, and gap junction communication were examined. Endothelial monolayers were treated with connexin-specific short interfering RNA (siRNA) and evaluated for communication, proliferation, and morphology under static and shear stress. Results show differential responses of Cx37, Cx40, and Cx43 to substrate and shear stress with reduced communication after shear exposure. RNA interference of individual connexins resulted in expression change of nontarget connexins, which suggests linked expression. Gap junction communication under static conditions is reduced following Cx43 siRNA treatment. Endothelial cells are more elongated with RNA interference (RNAi) targeting Cx40. In conclusion, endothelial connexins demonstrated novel sensitivity to mechanical environment and substrate. Individual isotypes show differential responses and RNAi knockdown provides new insight into connexin function and potential roles in the vasculature.
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PMID:Endothelial connexin 37, connexin 40, and connexin 43 respond uniquely to substrate and shear stress. 1792 38

Cellular interaction in blood vessels is maintained by multiple communication pathways, including gap junctions. They consist of intercellular channels ensuring direct interaction between endothelial and smooth muscle cells and the synchronization of their behavior along the vascular wall. Gap-junction channels arise from the docking of two hemichannels or connexons, formed by the assembly of six connexins, and achieve direct cellular communication by allowing the transport of small metabolites, second messengers, and ions between two adjacent cells. Physiologic variations in connexin expression are observed along the vascular tree, with most common connexins being Cx37, Cx40, and Cx43. Changes in the level of expression of connexins have been correlated to the development of vascular disease, such as hypertension, atherosclerosis, or restenosis. Recent studies on connexin-deficient mice highlighted key roles of these communication pathways in the development of these pathologies and confirmed the need for targeted pharmacologic approaches for their prevention and treatment. The aim of this issue is to review the current knowledge on the implication of gap junctions in vascular function and most common cardiovascular diseases.
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PMID:Connexins in vascular physiology and pathology. 1883 27

Endothelial cells (ECs) play many roles in vascular biology, including control of blood pressure, blood clotting, atherosclerosis, angiogenesis, and inflammation. Gap junctions (GJs) are channel-like assemblies of connexin (Cx) family proteins that connect neighboring cells and modulate and synchronize their intracellular environments by the transfer of intracellular mediators. It has been reported that vascular ECs express Cx37, Cx40, and Cx43, but not Cx32. Here, we showed that Cx32 mRNA and protein are expressed in various cultured human ECs. We confirmed Cx32 expression in blood vessel ECs using wild-type and Cx32 knock-out mice. We observed that dye transfer between cultured ECs through gap junctions is suppressed by an anti-Cx32 monoclonal antibody. These findings suggest that vascular ECs express Cx32, which participates in endothelial gap-junction intercellular communication.
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PMID:Connexin32 is expressed in vascular endothelial cells and participates in gap-junction intercellular communication. 1926 74

Connexins are members of a large family of transmembrane proteins that form hemichannels or gap junctions. These channels allow the exchange of ions and small metabolites between the cytosol and extracellular space or between neighboring cells. Connexins are important in vascular physiology; they support radial and longitudinal cell-to-cell communication in the vascular wall. Four connexins are expressed in the vascular wall: Cx37, Cx40, Cx43, and Cx45. Their expression is not uniform in all blood vessels and varies with vascular territory and species. Significant changes in the expression pattern of vascular connexins have been described during the development of atherosclerosis, a progressive inflammatory disease. In this review, we provide an overview of (1) the tools used to study the involvement of connexins in atherosclerosis, (2) the participation of connexins in atherogenesis, (3) the increasing interest of a polymorphism in the human connexin37 gene as marker of cardiovascular disease, and (4) the possible therapeutic implications of connexins.
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PMID:Connexins participate in the initiation and progression of atherosclerosis. 1940 45

Connexins are members of a large family of transmembrane proteins that oligomerize to form connexons or hemichannels, and connexons of adjacent cells dock to make gap junction channels. These channels allow the exchange of ions and small metabolites between the cytosol and extracellular space, or between the cytosols of neighbouring cells. Connexins are important in cardiovascular physiology; they support conducted vascular responses and allow for coordinated contraction of the heart. Four main connexins are expressed in the cardiovascular system: Cx37, Cx40, Cx43 and Cx45. Their expression pattern is not uniform and depends on intrinsic and environmental factors. Significant changes in the expression pattern, the cellular localization and the opening of connexin channels have been described during the development of atherosclerosis and after ischemia and reperfusion. In this review, we provide an overview of the roles of different connexins in these pathologies.
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PMID:Roles of connexins in atherosclerosis and ischemia-reperfusion injury. 2147 Jan 65

Atherosclerosis, a chronic inflammatory disease of the vessel wall, involves multiple cell types of different origins, and complex interactions and signaling pathways between them. Autocrine and paracrine communication pathways provided by cytokines, chemokines, growth factors and lipid mediators are central to atherogenesis. However, it is becoming increasingly recognized that a more direct communication through both hemichannels and gap junction channels formed by connexins also plays an important role in atherosclerosis development. Three main connexins are expressed in cells involved in atherosclerosis: Cx37, Cx40 and Cx43. Cx37 is found in endothelial cells, monocytes/macrophages and platelets, Cx40 is predominantly an endothelial connexin, and Cx43 is found in a large variety of cells such as smooth muscle cells, resident and circulating leukocytes (neutrophils, dendritic cells, lymphocytes, activated macrophages, mast cells) and some endothelial cells. Here, we will systematically review the expression and function of connexins in cells and processes underlying atherosclerosis. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.
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PMID:Connexins in atherosclerosis. 2260 70


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