Cardiovascular-derived therapeutic peptidomimetics in cardiovascular disease

Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality worldwide, posing huge financial and economic burdens and accounting for more than 17.8 million deaths in 2017. The medical costs of CVD in the US alone are estimated to be more than $350 billion per year ($214 billion in healthcare and $138 billion in lost job productivity) and are projected to increase to $749 billion in 2035. Peptides are a class of molecules that fall between small molecules and large biological molecules and are ubiquitous in cells and tissues where they mediate essential biological functions, such as signal transduction, growth, hemodynamic stability, and other homeostatic processes. Over the past five decades, there has been a rapid growth in the development of therapeutic peptides, with a dramatic increase in the number of peptide-based drugs on the market. There are over 60 peptide-based drugs approved for clinical use and about 150 peptides in clinical trials. Many peptides play a key role in the circulatory system both in health and disease. In this chapter, we provide an overview of current knowledge about cardiovascular-derived peptides—adrenomedullin, angiotensin II, endothelin, bradykinin, natriuretic peptides, and urotensin II—which play key roles as primary regulators of the cardiovascular system and have been implicated in the pathogenesis of CVDs including congestive heart failure, atherosclerosis, and coronary artery disease. We further focus on the physiological roles of these peptides in the cardiovascular system and their implications for CVDs. Better characterization of the molecular mechanisms of these peptides and their role in promoting cardiovascular damage will contribute to improving our overall understanding of the molecular basis of these diseases. Finally, we review applications of these peptides and/or their precursors as therapeutic agents for CVD.