Developmental endothelial locus-1 (DEL-1) protected mice from angiotensin II- and DOCA-salt-induced cardiovascular remodeling and progression of hypertension via immunomodulation.
Does developmental endothelial locus-1 (DEL-1) improve cardiovascular remodeling and hypertension in mouse models of hypertension?
DEL-1 protects against hypertension-induced cardiovascular remodeling and progression of hypertension via immunomodulation, suggesting its potential as a therapeutic target.
The causative role of inflammation in hypertension-related cardiovascular diseases is evident and calls for development of specific immunomodulatory therapies. We tested the therapeutic efficacy and mechanisms of action of developmental endothelial locus-1 (DEL-1), an endogenous antiinflammatory factor, in angiotensin II- (ANGII-) and deoxycorticosterone acetate-salt-induced (DOCA-salt-induced) cardiovascular organ damage and hypertension. By using mice with endothelial overexpression of DEL-1 (EC-Del1 mice) and performing preventive and interventional studies by injecting recombinant DEL-1 in mice, we showed that DEL-1 improved endothelial function and abrogated aortic adventitial fibrosis, medial thickening, and loss of elastin. DEL-1 also protected the mice from cardiac concentric hypertrophy and interstitial and perivascular coronary fibrosis and improved left ventricular function and myocardial coronary perfusion. DEL-1 prevented aortic stiffness and abolished the progression of hypertension. Mechanistically, DEL-1 acted by inhibiting αvβ3 integrin-dependent activation of pro-MMP2 in mice and in human isolated aorta. Moreover, DEL-1 stabilized αvβ3 integrin-dependent CD25+FoxP3+ Treg numbers and IL-10 levels, which were associated with decreased recruitment of inflammatory cells and reduced production of proinflammatory cytokines in cardiovascular organs. The demonstrated effects and immune-modulating mechanisms of DEL-1 in abrogation of cardiovascular remodeling and progression of hypertension identify DEL-1 as a potential therapeutic factor.
Failer et al. (Tue,) conducted a other in Hypertension-induced cardiovascular remodeling. Developmental endothelial locus-1 (DEL-1) vs. Vehicle or Fc control was evaluated on Cardiovascular remodeling and systolic blood pressure. Developmental endothelial locus-1 (DEL-1) protected mice from angiotensin II- and DOCA-salt-induced cardiovascular remodeling and progression of hypertension via immunomodulation.