Abstract

Cardiac hypertrophy is a major risk for the progression of heart failure; however, the underlying molecular mechanisms contributing to this process remain elusive. The caveolae microdomain plays pivotal roles in various cellular processes such as lipid homeostasis, signal transduction, and endocytosis, and also serves as a signaling platform. Although the caveolae microdomain has been postulated to have a major contribution to the development of cardiac pathologies, including cardiac hypertrophy, recent evidence has placed this role into question. Lack of direct evidence and appropriate methods for determining activation of caveolae-specific signaling has thus far limited the ability to obtain a definite answer to the question. In this review, we focus on the potential physiological and pathological roles of the multifunctional kinase Ca2+/calmodulin-dependent kinase II and voltage-dependent L-type calcium channel in the caveolae, toward gaining a better understanding of the contribution of caveolae-based signaling in cardiac hypertrophy.

Highlights

  • Caveolae are unique flask-like membrane invaginations of 50–80 nm in diameter, which are enriched in cholesterol and sphingolipids (Shaul and Anderson, 1998; Parton and Simons, 2007)

  • We have here summarized the current knowledge on the effects of caveolae-specific signal activation in relation to the pathogenesis of cardiac hypertrophy

  • The related molecules such as calmodulin-dependent kinase II (CaMKII) and L-type calcium channel (LTCC) have multiple cellular functions that seem to depend on the corresponding subcellular localization of the molecules, including intracellular organelles and microdomains

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Summary

Introduction

Caveolae are unique flask-like membrane invaginations of 50–80 nm in diameter, which are enriched in cholesterol and sphingolipids (Shaul and Anderson, 1998; Parton and Simons, 2007). Ca2+-dependent signaling molecules such as calcineurin and CaMKII play vital roles in the development of cardiac hypertrophy, and activation of these molecules is associated with LTCC activity (Anderson et al, 2011; Chen et al, 2011).

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