Conclusions

In this chapter we have reviewed the multitude of evidence that the structural protein caveolin-1 and the caveolae themselves are essential for the control of NO production. Although caveolin-deficient mice are viable, there are today clear insights on the deregulation, in these mice, of many biological functions wherein NO is a key mediator or modulator, including angiogenesis [46,47], vasodilation [48,49], vascular permeability [61,62], lipid metabolism [36], and cardiac biology [63,64]. More specifically, we have documented that the caveolar compartmen-tation of eNOS plays a paradoxical role, both tonically repressing basal eNOS activity by the enzyme's interactions with caveolin, and also ensuring the efficient activation of the enzyme upon agonist stimulation.

No other caveolar protein resident has been so extensively studied as eNOS. Although many studies remain to be performed to understand the relevance of the specific locale of the dozens of molecules proposed to be associated with caveolin, it can be stated that among the responses to the many incoming signals integrated in the caveolar organelles, endothelial NO production appears as one of the major signal emanating from these signaling platforms.

Abbreviations

APT1

acyl-protein thioesterase 1

CaM

calmodulin

CBM

caveolin binding motif

CSD

caveolin scaffolding domain

eNOS

endothelial nitric oxide synthase

FC

free cholesterol

GST

glutathione S-transferase

HDL

high-density lipoprotein

HMGCoA

hexamethylglutaryl coenzyme A

iNOS

inducible NOS isoform

mAchR

muscarinic cholinergic

NO

nitric oxide

NOSIP

eNOS interacting protein

NOSTRIN

eNOS traffic inducer

oxLDL

oxidized low-density lipoprotein

VEGF

vascular endothelial growth factor

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