MAF Transcription Factors: Emerging Key Players in Cardiovascular Health and Disease

Cardiovascular diseases are a leading cause of morbidity and mortality worldwide, and their complex pathophysiological mechanisms remain incompletely understood. The regulatory role of transcription factors provides a crucial avenue for investigating the mechanisms underlying these diseases. The MAF transcription factor family is a key member of the AP-1 superfamily, comprising two subfamilies: large MAFs (including MAFA, MAFB, MAF [c-MAF], and NRL) and small MAFs (including MAFK, MAFG, and MAFF). Different members exhibit distinct cellular expression patterns and functions within tissues: small MAFs members show high expression in cardiac tissue, participating in core pathological processes such as myocardial antioxidant stress, inflammatory response, and lipid metabolism disorders. They are closely associated with common cardiovascular diseases, including heart failure, myocardial fibrosis, atherosclerosis, and hypertrophic cardiomyopathy. Large MAFs are more widely distributed across other tissues and cell types. For instance, MAFB is primarily expressed in macrophages, pancreatic α-cells, neurons, and microglia. MAF regulates cell differentiation and immune responses in diverse tissues, including the lens, pancreas, and kidney. MAFA and NRL are specifically expressed in pancreatic β-cells and retinal photoreceptor cells, respectively. However, preliminary evidence suggests that large MAFs may play a significant role in maintaining physiological homeostasis and driving pathological progression within the cardiovascular system. Therefore, this review will first summarize research progress on small MAFs in the cardiovascular system, and then discuss the potential biological roles of large MAFs, particularly MAFB and MAF, in maintaining physiological homeostasis and driving pathological progression within the cardiovascular system. Finally, we lay out future paths for elucidating the roles of MAFs, particularly large MAFs, in the cardiovascular system.