Despite huge improvements in clinical diagnosis as well as numerous
options in patient care and treatment, the incidence of cardiovascular disease (CVD)
has been on the rise in the last decade potentially due to hitherto deteriorating lifestyle.
As a chronic inflammatory response of the arterial vessel wall, atherosclerosis and its
clinical sequelae such as coronary heart disease, cerebrovascular disease and peripheral
artery disease continue to be the leading causes of morbidity and mortality worldwide.
This makes it necessary to explore novel therapeutic strategies to control and
manipulate the mediators of atherosclerosis and cardiac repair processes in order to
help combat cardiovascular events. The complement system, an important part of the
innate immune response, constitutes a complex network of plasma proteins and
membrane cofactors which act in concert with other immunological systems of the
body for a rapid defense against foreign intrusions and infections. Activation of the
complement cascade in CVD is well established. Numerous well-conducted studies on targeting specific components of the complement cascade in CVD have opened
avenues for targeted pharmacological inhibition of the complement system at different
levels of complement activation. The use of gene targeting and neutralizing antibodies
as well as small molecule inhibitors in animal models of human CVD has provided a
clear beneficial role for blocking complement C5, C5a, C5a receptor (C5aR1, CD88)
and the soluble complement receptor 1 (sCR1) and different regulators at C3
convertase level. Moreover, the discovery of the second receptor for C5a, the C5aR2
(C5L2, C5a receptor-like 2) and recent studies on the functional role in atherosclerosis
has raised the intriguing possibility of the use of this receptor as a novel antiinflammatory
strategy. Though work is still in progress to determine whether there is a
global effect of this receptor in pathogenesis of cardiovascular disease, there is no
doubt that complement blocking strategies is an emerging field in medical
pharmacology.
Keywords: Atherosclerosis, Cardiac and vascular remodelling, Cardiovascular
disease, Complement inhibitors, Complement system and activation, Myocardial
infarction.
