Ghrelin As a Treatment for Cardiovascular Diseases
Ghrelin, a growth hormone–releasing peptide that was first discovered in the stomach of rats in 1999, is an endogenous ligand of growth hormone secretagogue receptors (GHSRs).1 Through binding to its receptors in the brain, ghrelin was initially shown to strongly stimulate the release of growth hormone and promote food intake.2 Subsequent studies revealed that GHSRs are expressed ubiquitously in many organs and tissues, and ghrelin functionally participates in the regulation of diverse processes including appetite control, energy balance, body weight maintenance, glucose and fat metabolism, cell proliferation, and apoptosis, as well as the modulation of gastrointestinal, cardiovascular, pulmonary, and immune functions.3,4 The primary receptor of ghrelin is currently thought to be GHSR1a; however, other unidentified receptors might exist.5,6 The high expression of GHSR1a in the heart and large vessels provides evidence of its cardiac activity,7 indicating ghrelin is a promising new therapeutic agent for cardiovascular diseases. In this review, we discuss some of the characteristic features of ghrelin treatment and its possible therapeutic roles in animals and patients afflicted with common cardiovascular diseases.
Production, Acylation, and Regulation
Ghrelin is produced predominantly in the stomach and is secreted from the submucosal layer into the bloodstream but not into the gastrointestinal tract. In situ analyses revealed that ghrelin and its mRNA are mainly localized in X/A-like cells, a major endocrine population in the gastric oxyntic mucosa that are morphologically similar to pancreatic α cells.1 Cells that produce low levels of ghrelin are also found in the lung, bowel, pancreas, kidney, placenta, testis, hypothalamus, pituitary gland, and the immune system.8–18 Ghrelin is reportedly produced in neoplastic tissues such as gastric and intestinal carcinoids and medullary thyroid carcinomas.19–21 In addition to endogenous ghrelin, growth hormone secretagogues, a heterogeneous group of synthetically produced …