Therapeutic potential of growth hormone-releasing hormone analogues in cardiovascular and cerebrovascular diseases: mechanisms and preclinical evidence.

Growth hormone-releasing hormone (GHRH) is a hypothalamic neuropeptide that stimulates growth hormone (GH) secretion from the pituitary gland, forming the central GHRH-GH-insulin-like growth factor-1 (IGF-1) endocrine axis. Beyond its classical endocrine function, GHRH and its receptors are widely expressed in extrapituitary tissues, where they regulate diverse physiological processes including cardiovascular function and neuroprotection. Preclinical studies demonstrate that synthetic GHRH analogues like MR-409 mitigate vascular calcification in diabetes, enhance cardiac repair post-myocardial infarction, and restore diastolic function in heart failure through calcium-handling modulation. In ischemic stroke models, MR-409 exhibits neuroprotective effects, reducing mortality and promoting neural regeneration. Studies performed in animal models have demonstrated the efficacy and therapeutic benefits of these compounds in diverse cardiomyopathies and ischemic stroke. Notably, these benefits occur independently of GH/IGF-1 signaling, highlighting their therapeutic potential for cardiovascular and cerebrovascular diseases. This narrative review synthesizes evidence from animal models, underscoring GHRH analogues as promising candidates for clinical translation. The articles included were identified through systematic searches in PubMed using keywords such as "GHRH analogues", "cardiovascular disease', and "ischemic stroke", with selection based on relevance to therapeutic applications and preclinical efficacy.