Cardiovascular disease.
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.
Severs
N J
NJ
National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Royal Brompton Hospital, London, UK.
D000595:Amino Acid Sequence; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D017630:Connexins / Q000276:immunology / Q000378:metabolism; D003331:Coronary Vessels / Q000293:injuries; D017629:Gap Junctions / Q000502:physiology*; D006321:Heart / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology
D017630:Connexins; D010455:Peptides