Stress response of nutrient-starved cardiovascular cells

Abstract

Both starvation and over-nutrition are conditions that exert nutrient stress on cardiovascular cells. Undernutrition results in reduced availability of micro- and macronutrients to all organ systems. However, studies have shown that overweight and obese individuals also have micronutrient deficiencies that contribute to the pathogenesis of cardiovascular disease. In utero nutrient deficiency negatively affects birth weight, total cholesterol, glucose tolerance, triglycerides, risk of coronary heart disease, and obesity. These effects are intergenerational. Some of the key signaling pathways responsible for these effects are discussed in this chapter. mTORC1 functions as a nutrient sensor; both overactivation of mTORC1 via over-nutrition and chronic suppression of mTORC1 causes cardiovascular stress and CVD. mTORC1 overactivation is well-addressed clinically via the development of inhibitors such as rapamycin. However, chronic suppression via inhibitors leads to suppressed expression of cardiac prosurvival proteins including MCL-1. Activation of the anti-inflammatory arm of the RAS (AT2R) via peptide agonist NP-6A4 restores MCL-1 and protects cardiomyocytes from nutrient stress.