Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels
Jun Yu, … , Radu V. Stan, William C. Sessa
Jun Yu, … , Radu V. Stan, William C. Sessa
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1284-1291. https://doi.org/10.1172/JCI27100.
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Research Article Hematology

Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels

Abstract

Caveolae in endothelial cells have been implicated as plasma membrane microdomains that sense or transduce hemodynamic changes into biochemical signals that regulate vascular function. Therefore we compared long- and short-term flow-mediated mechanotransduction in vessels from WT mice, caveolin-1 knockout (Cav-1 KO) mice, and Cav-1 KO mice reconstituted with a transgene expressing Cav-1 specifically in endothelial cells (Cav-1 RC mice). Arterial remodeling during chronic changes in flow and shear stress were initially examined in these mice. Ligation of the left external carotid for 14 days to lower blood flow in the common carotid artery reduced the lumen diameter of carotid arteries from WT and Cav-1 RC mice. In Cav-1 KO mice, the decrease in blood flow did not reduce the lumen diameter but paradoxically increased wall thickness and cellular proliferation. In addition, in isolated pressurized carotid arteries, flow-mediated dilation was markedly reduced in Cav-1 KO arteries compared with those of WT mice. This impairment in response to flow was rescued by reconstituting Cav-1 into the endothelium. In conclusion, these results showed that endothelial Cav-1 and caveolae are necessary for both rapid and long-term mechanotransduction in intact blood vessels.

Authors

Jun Yu, Sonia Bergaya, Takahisa Murata, Ilkay F. Alp, Michael P. Bauer, Michelle I. Lin, Marek Drab, Teymuras V. Kurzchalia, Radu V. Stan, William C. Sessa

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Figure 4

Cav-1 is necessary for flow-induced eNOS activation.

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Cav-1 is necessary for flow-induced eNOS activation. (A–D) Flow-induced ...
(A–D) Flow-induced dilations in pressurized isolated carotid arteries in the absence (circles) and presence (triangles) of l-NAME from WT (A; filled symbols; n = 4 and 10 with and without l-NAME, respectively), Cav-1 KO (B; open symbols; n = 4 and 8 with and without l-NAME, respectively), and Cav-1 RC mice (C; gray symbols; n = 4 and 6 with and without l-NAME, respectively). (D) Comparison of flow-induced dilation performed in the presence of l-NAME between the 3 strains (n = 4 per group). The responses to flow were similar between all groups of mice in the presence of L-NAME. *P < 0.05. (E) Basal eNOS phosphorylation on serine 1176 was reduced in Cav-1 KO mice and rescued in Cav-1 RC mice. Carotid arterial lysates were prepared as described in Methods, and densitometric evaluation of the normalized ratio of phosphorylated eNOS to total eNOS is shown below. (F) The localization of eNOS in intact carotid arteries was similar in WT, Cav-1 KO, and Cav-1 RC mice. Arrow reflects the direction of flow through the vessel segment.