Caveolin-3: therapeutic target for diabetic myocardial ischemia/reperfusion injury

Figures

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  Fig. 1. The cellular components’ distribution and structure of Cav-3. a. This diagram summarizes the cellular distribution of Cav-3. Cav-3 is transferred to plasma membrane after synthesis and processing in endoplasmic reticulum and Golgi, and it can also transfer to mitochondria and extracellular vesicles. b. This diagram shows the structure of caveolin oligomer and the main domains of Cav-3. Cav-3 has 151 amino acid residues and four main domains: IMD, CSD, OD, and SM. The OD, containing the CSD and SM, is represented with the dashed box. Caveolins can insert into plasma membrane via the IMD with their N- and C-terminal facing the cytoplasm. They are linked to each other through their OD domains to form a disc-shaped oligomeric complex on the membrane, and their C-terminals can be spirally assembled into barrel-like channels. The CSD is mainly responsible for the interaction of Cav-3 with other signaling molecules. IMD: intramembrane domain, CSD: caveolin scaffolding domain, OD: oligomerization domain, SM: signature motif

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  Fig. 2. Regulation of Cav-3 on oxidative stress, ER stress, mitochondrial homeostasis in diabetic myocardial I/R injury. This figure demonstrates that Cav-3 regulates oxidative stress, ER stress, mitochondrial homeostasis through a variety of signals to exert protective effects against myocardial I/R injury. Diabetes impairs myocardial Cav-3 expression, resulting in increased vulnerability to I/R injury. Cav-3: caveolin-3, ER: endoplasmic reticulum, FFAs: free fatty acids, PPARα: peroxisome proliferator-activated receptor α, AGEs: advanced glycation end products, RAGE: receptors for AGEs, Nrf2: nuclear factor erythroid 2-related factor 2, FAT10: F adjacent transcript 10, UPS: the ubiquitin-proteasome system, NO: nitric oxide, eNOS: endothelial NO synthase, PKA: protein kinase A, RORα: retinoic acid-related orphan nuclear receptor

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  Fig. 3. The regulation of autophagy, inflammation and apoptosis in diabetic myocardial I/R injury by Cav-3. This figure shows the regulatory roles of Cav-3 on multiple pathophysiological mechanisms in myocardial I/R injury, including autophagy, inflammation and apoptosis. The impaired expression of Cav-3 in diabetic hearts is a potential cause of more severe I/R injury. Cav-3: caveolin-3, Beclin1: Bcl-2-interacting protein1, Atg12: autophagy-related protein 12, FAT10: F adjacent transcript 10, ADRβ2: adrenergic receptor β2, cAMP: cyclic adenosine monophosphate, PKA: protein kinase A, BDNF: brain-derived neurotrophic factor, TrkB: tropomyosin-related kinase receptor B