Systemic chronic inflammation seen in cardiometabolic diseases, which confer significant morbidity and mortality worldwide, can induce macrophages to shift toward a pro-inflammatory phenotype in disease relevant tissues, e.g., the arterial wall in atherosclerosis. The mechanistic underpinnings of how macrophages shift phenotypes, an area for possible therapeutic targeting, remain incompletely understood; and a missing link is whether alternative splicing, which generates multiple protein isoforms, also contributes to the function of key proteins directly relevant to macrophage phenotypes and disease-relevant functions. The research outlined in this proposal will shed light on the possibility that alternative splicing modulates macrophage phenotype and function, providing a translational framework for future therapeutic targeting of the cardiometabolic diseasepromoting, pro-inflammatory macrophage.
|Effective start/end date||8/1/18 → 7/31/21|
- National Heart, Lung, and Blood Institute (5K08HL135348-04)