Therapeutic role of anti-inflammatory developmental endothelial locus-1 (Del-1) in angiotensin II-induced cardiovascular degeneration and hypertension
Final Report Abstract
High blood pressure or hypertension is defined as abnormal increase in arterial pressure. It remains a major health and socio-economic burden and is considered a non-infectious pandemic, as currently 1.5 billion people worldwide have hypertension. Fifty percent of adults aged over 55 years old are affected by hypertension in Germany. World health organisation labelled hypertension as silent killer, major public health concern. The label is adequate considering that the hypertension does not cause major symptoms but is number one cause of mortality worldwide. Cardiovascular diseases are major contributor to this mortality rates as hypertension is a major cause of cardiovascular morbidity and mortality. Although many anti-hypertensive drugs are available, one out of five patients has its arterial pressure under control. This disappointing fact is largely based on the lack of knowledge of pathophysiology of hypertension; therefore, treatment is not causal. To treat a cause of hypertension, mechanisms of its aetiology have to be understood. Immune system plays an important role in development of hypertension and cardiovascular diseases. Based on this, new therapeutic concepts emerged, potentially targeting immune system. Because of complexity and physiological importance of immune system, detailed immune mechanisms during hypertension have to be revealed before precisely and safely targeting the system in hypertension. We investigated the role of endogenous anti-inflammatory factor DEL-1, which is produced by endothelial cells. We used multiple models both mouse and human tissue to investigate its actions. We found that DEL-1 is a potent anti-inflammatory factor in hypertension, which protects from cardiovascular organ damage and abnormal progression of arterial pressure. DEL-1 inhibits inflammation during hypertension and protects from cardiac concentric hypertrophy and aortic stiffness. It also acts via inhibition of MMP2, enzyme responsible for the degradation of aortic elastic fibres leading to its stiffness. DEL-1 activates anti-inflammatory T cells, which further decrease adverse effects of immune system during hypertension. In conclusion, mechanisms of action of DEL-1 are immunomodulatory and not immunosuppressive, by that showing potential in decreasing detrimental immune response during hypertension and protecting from cardiovascular damage.
Publications
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Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation. Journal of Clinical Investigation, 132(6).
Failer, Theresa; Amponsah-Offeh, Michael; Neuwirth, Aleš; Kourtzelis, Ioannis; Subramanian, Pallavi; Mirtschink, Peter; Peitzsch, Mirko; Matschke, Klaus; Tugtekin, Sems M.; Kajikawa, Tetsuhiro; Li, Xiaofei; Steglich, Anne; Gembardt, Florian; Wegner, Annika C.; Hugo, Christian; Hajishengallis, George; Chavakis, Triantafyllos; Deussen, Andreas; Todorov, Vladimir & Kopaliani, Irakli
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Targeting inflammation in hypertension. Current Opinion in Nephrology & Hypertension, 32(2), 111-117.
Deussen, Andreas & Kopaliani, Irakli
