Caveolae, Lipid Rafts, and Vascular Disease

Li, Xiang-An; Everson, William V.; Smart, Elizabeth

doi:10.1016/j.tcm.2005.04.001

Cited by 92 publications

(63 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Formation and maintenance of lipid rafts and caveolae are strictly dependent on cholesterol. These specialized cholesterol-rich subdomains, highly abundant in endothelial cells, regulate various signal transduction pathways and are characterized by the presence of the caveolin protein family (Li et al, 2005). Treatment with statins reduces the amount of cholesterol in these sites, increases membrane fluidity, and induces a redistribution of caveolin-1 and other resident membrane proteins in the endoplasmic reticulum and plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Caveolin-1 is important for the biogenesis of caveolae and is also involved in cholesterol trafficking to and from plasma membrane. In fact, caveolin-1 directly binds cholesterol with high affinity, which can explain the high concentration of cholesterol in caveolae (Li et al, 2005). In particular, endothelial-specific overexpression of Cav-1 enhances the progression of atherosclerosis and loss of caveolae through Cav-1 gene deletion is protective against atherosclerosis (Frank et al, 2008;Ferná ndez-Hernando et al, 2010).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cholesterol-Lowering Drugs Inhibit Lectin-Like Oxidized Low-Density Lipoprotein-1 Receptor Function by Membrane Raft Disruption

Matarazzo¹,

Quitadamo²,

Mango³

et al. 2012

Mol Pharmacol

View full text Add to dashboard Cite

Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for oxidized low-density lipoprotein (ox-LDL) in endothelial cells, is up-regulated in atherosclerotic lesions. Statins are the principal therapeutic agents for cardiovascular diseases and are known to down-regulate LOX-1 expression. Whether the effect on the LOX-1 receptor is related to statinmediated cholesterol-lowering activity is unknown. We investigate the requirement of cholesterol for LOX-1-mediated lipid particle internalization, trafficking, and processing and the role of statins as inhibitors of LOX-1 function. Disruption of cholesterol-rich membrane microdomains by acute exposure of cells to methyl-␤-cyclodextrin or chronic exposure to different statins (lovastatin and atorvastatin) led to a spatial disorganization of LOX-1 in plasma membranes and a marked loss of specific LOX-1 function in terms of ox-LDL binding and internalization. Subcellular fractionation and immunochemical studies indicate that LOX-1 is naturally present in caveolae-enriched lipid rafts and, by cholesterol reduction, the amount of LOX-1 in this fraction is highly decreased (Ն60%). In contrast, isoprenylation inhibition had no effect on the distribution and function of LOX-1 receptors. Furthermore, in primary cultures from atherosclerotic human aorta lesions, we confirm the presence of LOX-1 in caveolae-enriched lipid rafts and demonstrate that lovastatin treatment led to down-regulation of LOX-1 in lipid rafts and rescue of the ox-LDL-induced apoptotic phenotype. Taken together, our data reveal a previously unrecognized essential role of membrane cholesterol for LOX-1 receptor activity and suggest that statins protect vascular endothelium against the adverse effect of ox-LDL by disruption of membrane rafts and impairment of LOX-1 receptor function.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cholesterol-Lowering Drugs Inhibit Lectin-Like Oxidized Low-Density Lipoprotein-1 Receptor Function by Membrane Raft Disruption

Matarazzo¹,

Quitadamo²,

Mango³

et al. 2012

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…Indeed, alteration/disruption of caveolin expression has been implicated, breast cancer [55][56][57], vascular abnormalities [58][59][60], pulmonary malfunction [33], and muscle disease [35,37].…”

Section: Caveolins: Important For the Trafficking And Clustering Of Mmentioning

confidence: 99%

Caveolin proteins and estrogen signaling in the brain

Luoma

Boulware

Mermelstein

2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Best described outside the nervous system, caveolins are structural proteins that form caveolae, functional microdomains at the plasma membrane that cluster related signaling molecules. Caveolin associated proteins include G protein coupled receptors and G proteins, receptor tyrosine kinases, as well as protein kinases, ion channels and various other signaling enzymes. Not surprisingly, a wide array of biological disorders are thought to be rooted in caveolin dysfunction. In addition, caveolins also traffic and cluster estrogen receptors to caveolae. Interactions between the estrogen receptors ERα and ERβ with caveolins appear critical in many non-neuronal cell types, e.g. disruption of normal function may underlie many forms of breast cancer. Recent findings suggest caveolins may also play an essential role in membrane estrogen receptor function in the nervous system. Not only are they expressed in neurons and glia, but different caveolin isoforms also appear necessary to generate distinct functional signaling complexes. With membrane estrogen receptors responsible for the efficient activation of a multitude of intracellular signaling pathways, which in turn influence a wide variety of nervous system functions, caveolin proteins are poised to act as the central coordinators of these processes.

show abstract

“…27 Recent studies using Cav1 Ϫ/Ϫ mice provided evidence supporting the physiological and pathophysiological importance of Cav1 in vivo. 15,17,22 Cav1 Ϫ/Ϫ mice show: (1) lack of caveolae in the tissues examined; (2) vascular dysfunction with impaired endothelium-dependent relaxation, contractility, and maintenance of myogenic tone; (3) hyperproliferation of mouse embryo fibroblasts in culture and hypercellularity of lung endothelial cells; (4) dilated cardiomyopathy and pulmonary hypertension, as well as cardiac hypertrophy; and (5) increased smooth muscle cell proliferation in a carotid artery blood flow cessation model. 28 -32 These studies suggest that Cav-1 normally functions as a negative regulator of cell growth.…”

Section: Lipid Rafts/caveolae and Caveolinsmentioning

confidence: 99%

“…7,10,13,14 Several recent reviews have described the physiological and pathophysiological roles of caveolae and caveolins in the cardiovascular system generally. [15][16][17][18] The main focus of this review is to summarize the recent progress on the emerging understanding of the role of Cav1 as a central organizer for the spatially and temporally regulated, ROS-dependent, growth-related AT 1 R signaling in VSMCs. …”

mentioning

confidence: 99%

Caveolin-Dependent Angiotensin II Type 1 Receptor Signaling in Vascular Smooth Muscle

Ushio‐Fukai

Alexander

2006

Hypertension

View full text Add to dashboard Cite

A ngiotensin II (Ang II) is a pluripotent hormone in vascular smooth muscle cells (VSMCs) and stimulates arterial hypertrophy, a hallmark of remodeling in hypertension. These effects are mediated primarily through the G protein-coupled receptor Ang II type 1 receptor (AT 1 R). 1 In VSMCs, AT 1 R-mediated signaling is biphasic, and internalization of the agonist/receptor complex into what we called a "signaling domain" is required for the tonic phase of signaling (initially characterized by phospholipase D activation) but not for the initial phospholipase C stimulation, which occurs at the cell surface. 2 This evidence was consistent with the existence of spatially discrete Ang II signaling domains. We showed that sequential Ang II-induced phospholipase activation is mediated through Ն2 G␣ subunits (G␣ q and G␣ 12/13 ), as well as their associated G␤␥ components. 3,4 In addition, various nonreceptor tyrosine kinases, including cAbl and some from the Src family, as well as mitogen-activated protein kinases and Akt, are activated by Ang II and mediate VSMC hypertrophy and growth. 5-7 Activation of these pathways is in part dependent on tyrosine phosphorylation (transmodulation) of the epidermal growth factor receptor (EGF-R), which serves as a "scaffold" for the assembly of cSrc and Pyk2, leading to downstream activation of extracellular-regulated kinase (ERK)1/2 and Akt. 8,9 These results are consistent with a model that requires temporal dispersion and organization of the AT 1 R signaling repertoire in VSMCs. 7,10 Accumulating evidence suggests that receptors and the signaling molecules with which they associate are not randomly distributed in the cell membrane but are localized in specialized signaling domains. Functionally distinct microdomains, formed by the lateral packing of glycosphingolipids and cholesterol within the membrane bilayer, have been identified in plasma membranes. These domains, called "lipid rafts," have been implicated in membrane trafficking and cellular signaling mechanisms and serve as "scaffolds" to facilitate the association of signaling complexes, thereby increasing the rate of interactions of receptors, coupling and adaptor molecules, and signaling proteins. 11 Caveolae are cell membrane invaginations that contain the major structural protein caveolin-1 (Cav1) and are thought to be subsets of rafts. They are postulated to be platforms for the coordination of certain signaling pathways. In VSMCs, Ang II stimulation promotes AT 1 R association with Cav1 and trafficking of the receptor from heavy density membrane fractions into relatively buoyant Cav1-enriched lipid rafts, which is required for transactivation of EGF-R at focal adhesions, another membrane signaling domains associated with growth factor and integrin signaling. 7,10,12,13 The full expression of the AT 1 R signaling repertoire depends on caveolae/lipid rafts and reactive oxygen species (ROS) production by reduced nicotinamideadenine dinucleotide phosphate (NADPH) oxidase. 7,10,13,14 Several recent reviews have described the...

show abstract

Caveolae, Lipid Rafts, and Vascular Disease

Cited by 92 publications

References 49 publications

Cholesterol-Lowering Drugs Inhibit Lectin-Like Oxidized Low-Density Lipoprotein-1 Receptor Function by Membrane Raft Disruption

Cholesterol-Lowering Drugs Inhibit Lectin-Like Oxidized Low-Density Lipoprotein-1 Receptor Function by Membrane Raft Disruption

Caveolin proteins and estrogen signaling in the brain

Caveolin-Dependent Angiotensin II Type 1 Receptor Signaling in Vascular Smooth Muscle

Contact Info

Product

Resources

About