Effect of mitochondrial DNA in inflammatory process in arterial hypertension: role of Toll like receptor 9

• Grant number: 12/11546-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2012
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Maria Helena Catelli de Carvalho
• Grantee: Gisele Facholi Bomfim
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Emerging evidence suggests that in addition of being the "power houses" of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mitochondrial DNA (mitDNA) that acts via Toll-like receptor 9 (TLR9), a pattern recognition receptor of the immune system, which detects bacterial and viral DNA but not vertebrate DNA. The ability of mitDNA to activate TLR9 in a similar fashion with bacterial DNA stems from evolutionary conserved similarities between bacteria and mitochondria. Mitochondrial DNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. In conditions as preeclampsia and trauma there is high level of mitDNA in plasma. In cardiovascular diseases, as arterial hypertension, the necrosis and vascular inflammation are constant contributing with formation of atherosclerotic plaques, vascular dysfunction and end organ lesion, however the etiology of these factors in hypertension is unknown. In view of these, our hypothesis is that the levels of mitDNA is increased in hypertensive animals and the mitDNA is a endogenous ligand that activate TLR9 in smooth muscle cells inducing a inflammatory response which contribute with vascular dysfunction and inflammation in hypertension.