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Review
. 2019 Jul 10:6:153.
doi: 10.3389/fmed.2019.00153. eCollection 2019.

Pathophysiological Role of Caveolae in Hypertension

Xiaoming Lian  1 , Claudia Matthaeus  2 , Mario Kaßmann  1 , Oliver Daumke  2 , Maik Gollasch  1   3
Affiliations
Review

Pathophysiological Role of Caveolae in Hypertension

Xiaoming Lian et al. Front Med (Lausanne). .

Abstract

Caveolae, flask-shaped cholesterol-, and glycosphingolipid-rich membrane microdomains, contain caveolin 1, 2, 3 and several structural proteins, in particular Cavin 1-4, EHD2, pacsin2, and dynamin 2. Caveolae participate in several physiological processes like lipid uptake, mechanosensitivity, or signaling events and are involved in pathophysiological changes in the cardiovascular system. They serve as a specific membrane platform for a diverse set of signaling molecules like endothelial nitric oxide synthase (eNOS), and further maintain vascular homeostasis. Lack of caveolins causes the complete loss of caveolae; induces vascular disorders, endothelial dysfunction, and impaired myogenic tone; and alters numerous cellular processes, which all contribute to an increased risk for hypertension. This brief review describes our current knowledge on caveolae in vasculature, with special focus on their pathophysiological role in hypertension.

Keywords: Ca2+ channels; caveolae; caveolin 1; endothelial nitric oxide synthase; hypertension.

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Figures

Figure 1
Figure 1
Model of caveolae. Caveolae model modified from Matthäus et al. (12). EHD2, Eps15 homology domain containing protein 2; Dyn2, Dynamin 2.
Figure 2
Figure 2
Schematic model of active eNOS in endothelial caveolae. Caveolae model modified from Matthäus et al. (12). M2-muscarinic acetylcholine receptor activation initiates an influx of Ca2+ that bind to calmodulin, eNOS dissociates from CBD of caveolin-1, CaM binds to eNOS, and the flow of electrons from NADPH to eNOS is restored, and then NO is produced. eNOS, endothelial nitric oxide synthase; NO, nitric oxide; CaM, calcium–calmodulin complex; CBD, caveolin scaffolding domain; ACh, acetylcholine; EHD2, Eps15 homology domain containing protein 2.
Figure 3
Figure 3
Schematic model of AngII-induced and mechanical stress-induced signaling pathway in vascular smooth muscle caveolae. Caveolae model modified from Matthäus et al. (12). Left: Ang II induces rapid translocation of AT1R to caveolae, AT1R and Caveolin 1 associate with each other. Caveolin 3 accompanies with AT1R. Right: Mechanical stress induces translocation of Caveolin 1 to non-caveolar sites and is associated with β1-integrins/Fyn/Shc to activate ERK signaling pathway. Cav1, Caveolin 1; Cav3, Caveolin 3; AngII, Angiotensin II; AT1R, AngII type1 receptor; ERK, extracellular signal-regulated kinase; Ca2+-permeable ion channels, such as TRPC, transient receptor potential channels, and EGFR, epidermal growth factor receptor.
Figure 4
Figure 4
Schematic model on the role of caveolae in Ca2+ signaling in vascular smooth muscle. L-type Cav1.2 channels in noncaveolar membrane sites and T-type Cav3.2 channels in caveolae produce Ca2+ influx into vascular SMCs to release Ca2+ sparks via ryanodine type 2 receptors (RyR) in the sarcoplasmic reticulum (SR). The Ca2+ sparks produce a negative-feedback effect on vasoconstriction by activating maxi Ca2+-activated K+ (BKCa) channels.
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