The role of complement in arterial hypertension and hypertensive end organ damage

Abstract

Increasing evidence indicates that hypertension and hypertensive end organ damage are not only mediated by hemodynamic injury but that inflammation plays an important role in the pathophysiology and contributes to the deleterious consequences of this disease. The complement system is an ancient part of innate immunity comprising multiple serum proteins and cellular receptors that protect the host from a hostile microbial environment and maintain tissue and cell integrity through the elimination of altered or dead cells. As an important effector arm of innate immunity, it plays also central roles in the regulation of adaptive immunity. Innate and adaptive immune responses have been identified as crucial players in the pathogenesis of arterial hypertension and hypertensive end organ damage. Thus, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses aside from direct effects on the vasculature. Indeed, recent experimental data strongly support a role for complement in all stages of arterial hypertension and hypertensive end organ damage. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest also a role for complement also in the development of malignant nephrosclerosis. We herein review the role of complement proteins in hypertension and hypertensive end organ damage.