BMAL1 in Ischemic Heart Disease: A Narrative Review from Molecular Clock to Myocardial Pathology

Abstract

The biological clock is crucial for controlling the circadian rhythm of the human body and maintaining the stable cyclic changes of various human life activities. Cardiovascular disease has become one of the primary problems affecting human life and health in today's society. Cardiovascular disease exhibits distinct circadian rhythms, with the core clock gene protein Brain and muscle ARNT-like protein 1 (BMAL1) playing critical roles in both physiological cardiac function and pathological processes. BMAL1 regulates myocardial gene expression, maintains normal structures, and stabilizes circadian rhythms to preserve cardiac homeostasis. In the pathological state of myocardial ischemia, BMAL1 ameliorates myocardial ischemic injury by regulating intrinsic mechanisms such as oxidative stress response, energy metabolism, immune-inflammatory response, and apoptosis and autophagy in cardiomyocytes. This review systematically examines BMAL1's involvement in myocardial ischemic injury through the circadian regulation of cardiac function. We analyze its multidimensional impacts on oxidative stress, energy metabolism, immune-inflammatory responses, apoptosis, and autophagy, highlighting the biological significance of this clock gene in ischemic pathophysiology.

Keywords: BMAL1; myocardial ischemia; time rhythm.

Figure 1

Regulatory mechanisms of myocardial ischemia by BMAL1. By Figdraw. BMAL1 (Brain and Muscle ARNT-like 1); CLOCK (Circadian Locomotor Output Cycles Kaput); Per (Period); Cry (Cryptochrome); Rev-Erbα (Nuclear Receptor Subfamily 1 Group D Member 1, NR1D1); RORA (Retinoic Acid Receptor-Related Orphan Receptor Alpha); ROS (Reactive Oxygen Species); HO-1 (Heme Oxygenase-1); NRF2 (Nuclear Factor Erythroid 2-Related Factor 2); AMPK (AMP-activated Protein Kinase); SIRT1 (Silent Information Regulator 1); PGC1α (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); ATP (Adenosine Triphosphate); Per2 (period circadian regulator 2); KLF15 (Krüppel-like Factor 15); NAMPT (Nicotinamide Phosphoribosyltransferase); NAD (Nicotinamide Adenine Dinucleotide); Pi3kr1 p85α (Phosphoinositide-3-Kinase Regulatory Subunit 1 p85α); AKT (Protein Kinase B); GSK3β (Glycogen Synthase Kinase 3 Beta); TLR9 (Toll-like Receptor 9); NF-kB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells); IGF2 (Insulin-like Growth Factor 2); TNF-α (Tumor Necrosis Factor Alpha); IL-1β (Interleukin-1 Beta); IL-6 (Interleukin-6); HDAC3 (Histone Deacetylase 3); ATG14 (Autophagy Related 14); PI3K (Phosphatidylinositol 3-Kinase); Akt (Protein Kinase B); EGLN2 (EGL homolog 2); PHD1 (Prolyl Hydroxylase Domain-containing Protein 1).

Figure 2

BMAL1’s regulatory role in the heart. By Figdraw.