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Vascular endothelial growth factor is crucial for cardiac homeostasis as a critical molecule in cardiac angiogenesis. Neuronal nitric oxide synthase is an essential enzyme producing nitric oxide, a key regulator of vascular tone. The present study aims to shed light upon the complex interactions between these three vital signaling molecules and examine their changes with the progression of hypertensive heart disease. We used two groups of spontaneously hypertensive rats and age\u2010matched Wistar rats as controls. The expression of the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase were assessed immunohistochemically. We used capillary density and cross\u2010sectional area of the cardiomyocytes as quantitative parameters of cardiac hypertrophy. Immunoreactivity of the molecules was more potent in both ventricles of spontaneously hypertensive rats compared with age\u2010matched controls. However, capillary density was lower in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. In addition, the cross\u2010sectional area of the cardiomyocytes was higher in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. Our study suggests a potential link between the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase in cardiac homeostasis and the hypertensive myocardium. Nevertheless, further research is required to better comprehend these interactions and their potential therapeutic implications.<\/jats:p>","DOI":"10.1002\/ar.25453","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T05:15:31Z","timestamp":1713158131000},"page":"3548-3563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The vascular footprint in cardiac homeostasis and hypertensive heart disease\u2014A link between apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase"],"prefix":"10.1002","volume":"307","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6971-8086","authenticated-orcid":false,"given":"Alexandar","family":"Iliev","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology Medical University of Sofia  Sofia 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