Caveolae and endothelial dysfunction: filling the caves in cardiovascular disease.
Discovery in the early 1990s of caveolin-1, the structural protein responsible for maintaining the ohm shape of caveolae, greatly enhanced investigations to elucidate the role of these little caves in the plasma membrane. Perhaps one of the most important realizations concerning caveolae and caveolin is that these elements play an important functional role in the modulation of cell signal transduction pathways, including those involved in endothelial nitric oxide synthase (eNOS) function. Their role was confirmed by studies with caveolin-1 knockout mice which lack caveolae and display abnormal endothelial function responses. One limitation of these knockout models, however, is that absence of the caveolin protein not only results in the lack of caveolae as a structure but also in the lack of interaction/modulation of enzymes/molecules (e.g. eNOS) to which caveolin binds (whether in- or outside caveolae). In contrast to caveolin knockout models, recent experimental findings suggest that in certain cardiovascular diseases caveolin may dissociate from caveolae to the cytosol, hence decreasing the number of caveolae without a change in the total amount of caveolin. Therefore, as the importance of defining the role of caveolins both in caveolae and in cellular regions is being highlighted, it seems also important at the same time to further define the role of caveolae per se being present in the plasma membrane as a structural entity. The objective of this review is to make an explorative tour on the role of caveolae in vascular endothelial function based on existing literature together with some preliminary experimental findings. Evidence and arguments are put forward that alterations in endothelial caveolae do occur in cardiovascular disease and may contribute to the observed endothelial dysfunction in these conditions.
Xu
Ying
Y
Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, The Netherlands.
Buikema
Hendrik
H
van Gilst
Wiek H
WH
Henning
Rob H
RH
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D021941:Caveolae / Q000187:drug effects / Q000502:physiology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism
D001685:Biological Factors; D051242:Caveolin 1; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D002784:Cholesterol; D002118:Calcium