Obesity and Clonal Hematopoiesis of Indeterminate Potential: Allies in Cardiovascular Diseases and Malignancies

Abstract

The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP is remarkably higher than the influence ascribed to hematologic malignancies, and it is plausible that cardiovascular diseases (CVD) could elucidate the apparent disparity. Studies have shown that the most frequently altered genes in CHIP are associated with the increased incidence of CVDs, type 2 diabetes mellitus (T2DM) and myeloid malignancies, as well as obesity. Additionally, multiple research studies have confirmed that obesity is also independently associated with these conditions, particularly the development and progression of atherosclerotic CVD. Considering the shared pathogenetic mechanisms of obesity and CHIP, our objective in this review was to investigate both preclinical and clinical evidence regarding the correlation between obesity and CHIP and the resulting implications of this interaction on the pathophysiology of CVDs and malignancies. The pro-inflammatory condition induced by obesity and CHIP enhances the probability of developing both diseases and increases the likelihood of developing CVDs, T2DM and malignancies, suggesting that a dangerous vicious loop may exist. However, it is vital to conduct additional research that will suggest targeted treatment options for obese individuals with CHIP in order to reduce harmful effects connected to these conditions.

Keywords

• obesity
• clonal hematopoiesis of indeterminate potential
• CHIP
• cardiovascular disease
• malignancy
• leukemia