CONCOMITANCE OF ENDOTHELIUM DISORDERS IN THE BRAIN AND HEART VESSELS IN ISCHEMIC HEART DISEASE

Introduction. Endothelial dysfunction (ED) is a key pathogenetic mechanism underlying cardiovascular and cerebrovascular diseases and is increasingly recognized as a common link between ischemic heart pathology and cerebral vascular impairment. In addition to postnatal risk factors, adverse intrauterine conditions, particularly prenatal hypoxia (PH), may program long-term endothelial alterations. The aim of this study was to investigate the structural and molecular features of ED in the myocardial and cerebral vessels in experimental chronic heart failure (CHF) and PH, as well as to evaluate the endothelioprotective potential of pharmacological agents targeting the nitric oxide system.

Methods. This study was conducted on Wistar rats using experimental models of CHF (doxorubicin administration, cumulative dose 15 mg/kg) and PH (sodium nitrite 50 mg/kg administered to pregnant females on gestational days 16–21). The endothelial status of cerebral and myocardial vessels was assessed using immunohistochemistry, ELISA, morphometric analysis, and real-time PCR. Key markers of endothelial function, inflammation, nitric oxide metabolism, oxidative stress, and angiogenesis were evaluated. The endothelioprotective potential of nitric oxide-modulating pharmacological agents was also evaluated.

Results. CHF and PH induced pronounced structural and functional endothelial alterations in the microcirculatory and muscular-type vessels of the heart and brain. These changes were characterized by reduced endothelial cell density, suppressed eNOS expression, increased iNOS expression, nitric oxide deficiency, elevated nitrotyrosine levels, and activation of proinflammatory cytokines. VEGF levels were significantly decreased, while apoptotic features of endothelial cells were intensified. Angiolin and Hypertril demonstrated the most pronounced endothelioprotective effects among the tested agents.

Conclusions. CHF and PH induce persistent ED in cerebral and myocardial vessels through disruption of the nitric oxide system, oxidative stress, and inflammatory activation. PH may act as an early trigger increasing susceptibility to cardiovascular and cerebrovascular diseases later in life. These findings support the rationale for targeted endothelioprotective therapy in ischemic cardiovascular pathology.