A6321 Complement in Hypertension and Target Organ Damage

Abstract

Objectives: Immunity and inflammation play pivotal roles in the development of hypertension, including innate and adaptive immunity. Complement system provides a bridge between innate and adaptive immune cells. We aim to elucidate the mechanism of complement activation in hypertension and related target organ damage. Methods: Complement C3, C3aR, C5aR knock out (KO) mice were utilized for performing hypertension model, including deoxycorticosterone acetate (DOCA)/salt and angiotensin II (Ang II)-induced hypertension. Macrophage and T cells were separated for stimulating with complement factors. Results: We firstly found that perivascular adipose tissue (PVAT) expressed abundant C3, which stimulated adventitial fibroblast migration and phenotype transdifferentiation. Subsequently, we showed that C5a regulated M1/M2 macrophage polarization and inhibited adiponectin production in the PVAT, which contributed to vascular inflammation in hypertension. More important, we demonstrated that double C3aR and C5aR KO (DKO) prevented Ang II-induced blood pressure elevation. Mechanically, DKO activated the immunosuppressive functio of regulatory T cells (Tregs). Adoptive transfer of DKO Tregs attenuated Ang II-induced hypertension and target organ damage. Conclusion: Our results demonstrate that complement activation-mediated immune cell infiltration is involved in the development of hypertension and target organ damage. Blockade of complement activation may be an alternative novel approach for hypertension treatment.