Abstract
The mechanisms committed in the activation and response of vascular and inflammatory immune cells play a major role in tissue remodeling in cardiovascular diseases (CVDs) such as atherosclerosis, pulmonary arterial hypertension, and abdominal aortic aneurysm. Cardiovascular remodeling entails interrelated cellular processes (proliferation, survival/apoptosis, inflammation, extracellular matrix (ECM) synthesis/degradation, redox homeostasis, etc.) coordinately regulated by a reduced number of transcription factors. Nuclear receptors of the subfamily 4 group A (NR4A) have recently emerged as key master genes in multiple cellular processes and vital functions of different organs, and have been involved in a variety of high-incidence human pathologies including atherosclerosis and other CVDs. This paper reviews the major findings involving NR4A3 (Neuron-derived Orphan Receptor 1, NOR-1) in the cardiovascular remodeling operating in these diseases.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated of more than 17 million lives each year (18.6 million (33.6% of all deaths worldwide) according to the 2019 Global Burden of Disease (GBD) Study update) [1]
NOR-1 is further induced in endothelial cells exposed to hypoxia, primarily through a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism involving an increase in both, cytosolic Ca2+ and the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway [32], and the binding of HIF-1 to a Hypoxia Response Element (HRE) present in its proximal promoter region
The nuclear receptor NOR-1 seems to play a relevant role in regulating the function of vascular cells, cardiomyocytes, and inflammatory cells and the immune response in cardiovascular remodeling underlying atherosclerosis, abdominal aortic aneurysm (AAA), pulmonary artery hypertension, and cardiac hypertrophy
Summary
Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated of more than 17 million lives each year (18.6 million (33.6% of all deaths worldwide) according to the 2019 Global Burden of Disease (GBD) Study update) [1]. Atherosclerosis, as the common pathological substrate of ischemic heart disease (IHD) and ischemic cerebrovascular disease, is responsible for a striking reduction in quality of life and life expectancy and imposes huge costs on health systems worldwide. Cardiovascular remodeling is a complex response that involves several cell types and interrelated processes (inflammation, extracellular matrix (ECM) remodeling, altered calcium and redox homeostasis, apoptosis, etc.), activated by intricate gene programs orchestrated by a reduced number of transcription factors. Nuclear receptors (NRs) are master regulators of a plethora of cellular and biological processes such as cell proliferation, migration, apoptosis, metabolism, and differentiation. This paper reviews the major findings involving NR4A3 (NOR-1) in atherosclerosis and other CVDs
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