Calcitriol Supplementation Protects Against Apoptosis and Alleviates the Severity of Abdominal Aortic Aneurysm Induced by Angiotensin II and Anti-TGFβ

• Published in: Journal of cardiovascular translational research Vol. 15; no. 6; pp. 1340 - 1351
• Main Authors: Jreije, Afaf, Medlej-Hashim, Myrna, Hajal, Joelle, Saliba, Youakim, Chacar, Stephanie, Fares, Nassim, Khouzami, Lara
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2022
• Subjects: Angiotensin II - adverse effects; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - diagnostic imaging; Aortic Aneurysm, Abdominal - prevention & control; Apoptosis; Biomedical Engineering and Bioengineering; Biomedicine; Calcitriol - pharmacology; Calcitriol - therapeutic use; Cardiology; Dietary Supplements; Disease Models, Animal; Human Genetics; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-E2-Related Factor 2 - metabolism; Original Article; Transforming Growth Factor beta - antagonists & inhibitors; Caspase; Vitamin D deficiency; Cu/Zn-SOD; Nrf2; Abdominal aortic aneurysm; Calcitriol
• ISSN: 1937-5387; 1937-5395
• DOI: 10.1007/s12265-022-10254-9

The present study aims to assess the effect of vitamin D deficiency (VDD) and its supplementation on the severity of AAA in mice. AAA was induced by AngII and anti-TGF-β administration. Animals were divided into four groups: Sham, mice with AAA, mice with AAA, and VDD, and mice with AAA supplemented with calcitriol. Blood pressure, echocardiography, abdominal aortic tissues, and plasma samples were monitored for all groups. VDD was associated with enhanced activity of cleaved MMP-9 and elastin degradation and positively correlated with the severity of AAA. Calcitriol supplementation decreased the INFγ/IL-10 ratio and enhanced the Nrf2 pathway. Moreover, Cu/Zn-superoxide dismutase expression and catalase and neutral sphingomyelinase activity were exacerbated in AAA and VDD groups. Furthermore, calcitriol supplementation showed a significantly lower protein expression of caspase-8, caspase-3, Bid, and t-Bid, and prevented the apoptosis of VSMCs treated by AngII and anti-TGF-β. Calcitriol supplementation may alleviate AAA severity and could be of great interest in the clinical management of AAA. Graphical abstract VDD enhances antioxidant enzymes activity and expression, whereas calcitriol supplementation alleviates AAA severity by re-activating Nrf2 and inhibiting apoptotic pathways.