TY - JOUR
T1 - Pathogenic role of complement in arterial hypertension and hypertensive end organ damage
AU - Wenzel, Ulrich O.
AU - Bode, Marlies
AU - Köhl, Jörg
AU - Ehmke, Heimo
PY - 2017/3/1
Y1 - 2017/3/1
N2 - The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important 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. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.
AB - The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important 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. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.
UR - http://www.scopus.com/inward/record.url?scp=85014472677&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00759.2016
DO - 10.1152/ajpheart.00759.2016
M3 - Scientific review articles
C2 - 27986662
AN - SCOPUS:85014472677
SN - 0363-6135
VL - 312
SP - 349
EP - 354
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3
ER -