Role of Specificity Protein 1 (SP1) in Cardiovascular Diseases: Pathological Mechanisms and Therapeutic Potentials

Abstract

In mammals, specificity protein 1 (SP1) was the first Cys2-His2 zinc finger transcription factor to be isolated within the specificity protein and Krüppel-like factor (Sp/KLF) gene family. SP1 regulates gene expression by binding to Guanine-Cytosine (GC)-rich sequences on promoter regions of target genes, affecting various cellular processes. Additionally, the activity of SP1 is markedly influenced by posttranslational modifications, such as phosphorylation, acetylation, glycosylation, and proteolysis. SP1 is implicated in the regulation of apoptosis, cell hypertrophy, inflammation, oxidative stress, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, calcification, and other pathological processes. These processes impact the onset and progression of numerous cardiovascular disorders, including coronary heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, and vascular disease. SP1 emerges as a potential target for the prevention and therapeutic intervention of cardiac ailments. In this review, we delve into the biological functions, pathophysiological mechanisms, and potential clinical implications of SP1 in cardiac pathology to offer valuable insights into the regulatory functions of SP1 in heart diseases and unveil novel avenues for the prevention and treatment of cardiovascular conditions.

Keywords: SP1; arrhythmia; cardiomyopathy; cardiovascular disease; coronary heart disease; ischemia-reperfusion injury.

Figure 1

Structure of the SP1 gene. Different colors indicate various conserved domains, including the transcriptional activation domain, DNA-binding domain, Btd (buttonhead) box, and Sp box. The specific domain and unique biological functions are annotated.

Figure 2

The role of SP1 in gene transcription regulation. SP1 can either stimulate or suppress gene transcription by binding to Guanine–Cytosine (GC)-rich regions within target gene promoters or through post-translational modifications such as phosphorylation. SP1 is crucial in controlling processes such as apoptosis, cell hypertrophy, autophagy, inflammation, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, and other pathological pathways. These processes significantly influence the development and progression of pathological conditions such as coronary atherosclerotic heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, and vascular calcification. The straight arrows indicate the promotion of SP1 expression, while the T-shaped ends indicate inhibition. The red arrow represents target gene promoters.