Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Int J Mol Sci. 2021 Jul 21;22(15):7775. doi: 10.3390/ijms22157775.

Abstract

The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.

Keywords: PPAR; RXR; atherosclerosis; cardiomyocyte; cardiovascular disease; heart; myocardial infarction; nuclear receptors; transcription.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology*
  • Cardiovascular Physiological Phenomena*
  • Gene Expression Regulation*
  • Humans
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Receptors, Cytoplasmic and Nuclear