Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Considerable efforts are needed to elucidate the underlying mechanisms for the prevention and treatment of CVDs. Regulator of calcineurin 1 (RCAN1) is involved in both development/maintenance of the cardiovascular system and the pathogenesis of CVDs. RCAN1 reduction protects against atherosclerosis by reducing the uptake of oxidized low-density lipoproteins, whereas RCAN1 has a protective effect on myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma/aortic rupture mainly mediated by maintaining mitochondrial function and inhibiting calcineurin and Rho kinase activity, respectively. In this review, the regulation and the function of RCAN1 are summarized. Moreover, the dysregulation of RCAN1 in CVDs is reviewed. In addition, the beneficial role of RCAN1 reduction in atherosclerosis and the protective role of RCAN1 in myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma /aortic rupture are discussed, as well as underlying mechanisms. Furthermore, the therapeutic potential and challenges of targeting RCAN1 for CVDs treatment are also discussed.
Highlights
Cardiovascular diseases (CVDs), including heart and vascular disorders, are major causes of mortality and disability globally, especially in developed countries
regulator of calcineurin 1 (RCAN1) reduction is beneficial to atherosclerosis (MendezBarbero et al 2013) whereas RCAN1 protects against myocardial ischemia/reperfusion injury (Rotter et al 2014), myocardial hypertrophy (Sussman et al 1998) and intramural hematoma /aortic rupture (Villahoz et al 2018)
Rcan1 deletion can significantly decrease CD36 level in the aortic arches while complementary expression of both Rcan1.1 and Rcan1.4 could concomitantly increase the numbers of Oxidized LDL (oxLDL) particles taken up by macrophages, indicating the protective effect of RCAN1 downregulation on atherosclerosis might be mediated by CD36 reduction (Mendez-Barbero et al 2013)
Summary
Cardiovascular diseases (CVDs), including heart and vascular disorders, are major causes of mortality and disability globally, especially in developed countries. Accumulated evidence indicates that regulator of calcineurin 1 (RCAN1) plays pivotal roles in the pathogenesis of CVDs and may be a potential therapeutic target. It indicates that RCAN1 plays a complex role in regulating calcineurin-NFAT signaling, depending on both the dosage of RCAN1 and the environmental levels of AngII, PDGF and ISO.
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