Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

PURPOSE: Radiotherapy is a major pillar in the treatment of solid tumors including breast cancer. However, epidemiological studies have revealed an increase in cardiac diseases approximately a decade after exposure of the thorax to ionizing irradiation, which might be related to vascular inflammation. Therefore, chronic inflammatory effects were examined in primary heart and lung endothelial cells (ECs) of mice after local heart irradiation. METHODS: Long-lasting effects on primary ECs of the heart and lung were studied 20-50 weeks after local irradiation of the heart of mice (8 and 16 Gy) in vivo by multiparameter flow cytometry using antibodies directed against cell surface markers related to proliferation, stemness, lipid metabolism, and inflammation, and compared to those induced by occlusion of the left anterior descending coronary artery. RESULTS: In vivo irradiation of the complete heart caused long-lasting persistent upregulation of inflammatory (HCAM, ICAM­1, VCAM-1), proliferation (CD105), and lipid (CD36) markers on primary heart ECs and an upregulation of ICAM­1 and VCAM­1 on primary ECs of the partially irradiated lung lobe. An artificially induced heart infarction induces similar effects with respect to inflammatory markers, albeit in a shorter time period. CONCLUSION: The long-lasting upregulation of prominent inflammatory markers on primary heart and lung ECs suggests that local heart irradiation induces chronic inflammation in the microvasculature of the heart and partially irradiated lung that leads to cardiac injury which might be related to altered lipid metabolism in the heart.

Gingko biloba extract EGB761 alleviates heat-stress damage in chicken heart tissue by stimulating Hsp70 expression in vivo in vascular endothelial cells.

1. This study aimed to investigate the protective effects of Gingko biloba extract EGB761 on heat-stressed chicken heart in vivo and its underlying relevance to Hsp70.2. A total of 50 one-day-old female chicks were randomly divided into five groups: control (Con), heat-stress (HS), 0.1% EGB761 plus heat-stress (0.1%EGB+HS), 0.3%EGB761 plus heat-stress (0.3%EGB+HS) and 0.6%EGB761 plus heat-stress (0.6%EGB+HS) groups. After administration of EGB761 for 45 days, the chickens in each group were exposed to a single heat-stress event at 38 ± 1°C for 3 h.3. EGB761 attenuated the abnormal symptoms and pathological scores of myocardium of heat-stressed chickens. Despite a reduction in the transcription and translation of the Hsp70 gene in heat-stressed myocardium, EGB761 induced the expression of Hsp70 in endothelial cells of the microarteries and venules into the blood, and reduced heat-stress damage in vascular endothelial cells.4. Supplementation with EGB761 before heat-stress exposure protected chicken myocardium from damage by increasing serum Hsp70 protein from myocardial cells and cardiac microvascular endothelial cells and protected the microvascular system from adverse injury.

Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice.

Aging results in functional and structural changes in the cardiovascular system, translating into a progressive increase of mechanical vessel stiffness, due to a combination of changes in micro-RNA expression patterns, autophagy, arterial calcification, smooth muscle cell migration and proliferation. The two pivotal mechanisms of aging-related endothelial dysfunction are oxidative stress and inflammation, even in the absence of clinical disease. A comprehensive understanding of the aging process is emerging as a primary concern in literature, as vascular aging has recently become a target for prevention and treatment of cardiovascular disease. Change of life-style, diet, antioxidant regimens, anti-inflammatory treatments, senolytic drugs counteract the pro-aging pathways or target senescent cells modulating their detrimental effects. Such therapies aim to reduce the ineluctable burden of age and contrast aging-associated cardiovascular dysfunction. This narrative review intends to summarize the macrovascular and microvascular changes related with aging, as a better understanding of the pathways leading to arterial aging may contribute to design new mechanism-based therapeutic approaches to attenuate the features of vascular senescence and its clinical impact on the cardiovascular system.