Noncardiovascular-derived therapeutic peptidomimetics in cardiovascular disease

Cardiovascular diseases (CVDs) make up a group of heart and blood vessel disorders and remain the most common cause of death worldwide. Annually, approximately one in every six US healthcare dollars is spent on CVD, and by 2035 the number of Americans with CVD is anticipated to rise to 131.2 million—45% of the total US population. Peptides are naturally occurring short chains of amino acids, typically comprising 2–50 amino acids and ubiquitously found in all living organisms, which display a large diversity of biological effects that regulate most physiological processes. Since the isolation of insulin, which later became the first commercially available peptide drug, peptide therapeutics have played important roles in medical practice. Over the years, there has been a constant increase in the number of peptides entering clinical studies. Importantly, peptides demonstrate higher success rates in transitioning from phase 1 to phase 2 trials as compared to small molecules and biological drugs, and in transitioning from phase 3 to regulatory review. This chapter discusses the therapeutic potential of peptides which primarily affect organ systems other than the cardiovascular system (CVS), but which also play key roles in the CVS. For example, the neurohormones vasopressin and oxytocin, which primarily control endocrine and reproductive processes, were recently found to have cardioprotective properties. The vasodilatory and other cardiovascular effects of calcitonin gene-related protein, vasoactive intestinal peptide, amylin and glucagon-like peptide-1, and the potential cardioprotective effects of ghrelin, salusin, apelin, and urocortin are also reviewed. Together, through their gastrointestinal or neuronal actions, these noncardiovascular peptides play roles in the regulation of normal cardiovascular hemodynamics and may be used to reduce CVD-related morbidity and mortality.