Interplay between Clonal Hematopoiesis of Indeterminate Potential and Metabolism. (July 2020)

• Record Type: Journal Article
• Authors: Lee, Man K.S.; Dragoljevic, Dragana; Bertuzzo Veiga, Camilla; Wang, Nan; Yvan-Charvet, Laurent; Murphy, Andrew J.
• Is Part Of: Trends in endocrinology and metabolism. Volume 31:Number 7(2020)
• Page Start: 525
• Page End: 535
• Publication Date: 2020-07
• Subjects: diabetes -- cardiovascular disease -- clonal hematopoiesis of indeterminant potential -- metabolism -- inflammation; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2020.02.005
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Clonal hematopoiesis of indeterminate potential (CHIP), defined as a clone of hematopoietic cells consisting of a single acquired mutation during a lifetime, has recently been discovered to be a major risk factor for atherosclerotic cardiovascular disease (CVD). As such, this phenomenon has sparked interest into the role that these single mutations may play in CVD. Atherosclerotic CVD is a complex disease and we have previously shown that atherosclerosis can be accelerated by metabolic- or autoimmune-related risk factors such as diabetes, obesity, and rheumatoid arthritis. In this review, we discuss the role of CHIP, the interplay between CHIP and metabolic diseases, as well as how metabolism of hematopoietic stem cells (HSCs) could regulate CHIP-related HSC fate. Highlights: Clonal hematopoiesis of indeterminate potential (CHIP) arises from the outgrowth of a single clone driven by one somatic mutation in HSCs, without developing any hematological abnormalities. Emerging evidence suggests that people with CHIP have an increased risk for atherosclerotic cardiovascular disease. Recent studies have investigated the role and function of CHIP-related genes. The most widely studied CHIP gene in atherosclerosis is TET2 . In animal models of atherosclerosis, it has been shown that the loss of TET2 in HSCs contributes to increased skewing of monocytes, a key contributor to atherogenesis. There are close links between cellular metabolism and the function/regulation of a number of the genes mutated in CHIP. For example, the activity of TET2 is modulated by the cofactor α-ketoglutarate, a key intermediate in the TCA cycle. In addition to acting as metabolic sensors, AMPK and SIRT1 are important in regulating the activity of TET2. Moreover, vitamin C can be metabolized to directly impact TET2 function.