Clonal hematopoeisis and inflammatory mechanisms in cardiovascular disease

Cardiovascular diseases (CVD) are the manifestations of chronic inflammation facilitated by aging, diabetes, dyslipidemia, hypertension, and smoking. These conditions promote atherosclerosis and fibrosis in the heart. Utilization of anti-inflammatory therapeutics can decrease death and mortality from cardiovascular disease and slow progression of heart failure. It therefore implicates inflammation to be causal in the development of CVD. As such, novel studies exploring the cardiovascular-immune interface are needed for improved therapeutic options.

One striking example of a condition that is causal for CVD is clonal hematopoiesis of indeterminate potential (CHIP).  CHIP is a common age-related condition. CHIP occurs when a hematopoietic stem cell develops a somatic mutation in a driver gene that confers a survival or proliferative advantage to its daughter cells.  While there is no skewing of haematological lineages that develops from the mutation, a striking pro-inflammatory phenotype emerges. The mechanisms by which this happens remains unclear. It is also uncertain as to whether the mutated cells are causing the disease or whether these cells stimulate non-mutated cells to become more inflamed.

We are therefore exploring novel mechanisms in inflammation, which include cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, genetic susceptibility, obesity, and other stimulators of such events.

These studies require a highly multidisciplinary setting, including molecular biology, cardiology, hematology, genetics and bioinformatics.  Importantly, the advanced and technical studies of clonal hematopoiesis of indeterminate potential and similar inflammatory mechanisms driving cardiovascular disease are uniquely suited to set the standards by which cardiology may utilize personalized medicine in the coming decades.

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