Renin inhibition reduces atherosclerotic plaque neovessel formation and regresses advanced atherosclerotic plaques

Cathepsin K activity controls cardiotoxin‐induced skeletal muscle repair in mice

“…Initially, cathepsins were recognized to function as scavengers for protein recycling in lysosomes and endosomes of mammalian cells under physiological and pathological conditions . However, the recognition of the cysteinyl cathepsins led to the exploration of their functions in metabolic and inflammatory cardiovascular disorders . Like the members of the MMP family, most of the cathepsins have been shown to be regulatory exoproteases that are widely expressed in various tissues or cells by inflammatory cytokines and growth factors .…”

Can renin inhibition by Aliskiren prove itself in atherosclerosis prevention?

“…In this issue of Atherosclerosis Wu and colleagues [6] investigate the effect of RAAS inhibition by Aliskiren on neovessel formation and atherosclerotic plaque development in an apolipoprotein Edeficient (ApoE À/À) mouse model of late atherosclerosis. The key feature of this study is a roughly 54% reduction of intima/media ratio as indicator of plaque size as well as a significant reduction of neovascularization in aortic roots of Aliskiren-treated mice in a blood pressure-independent matter.…”

“…The physiological process of new vessel formation restores normoxia in the vessel wall, whereas pathologically increased neovascularization leads to the vicious cycle of disease progression by inflammation, wall thickening and hypoxia [7]. Wu et al [6] further found an increased collagen and elastin plaque content indicating a more stable plaque, while macrophage infiltration, the expression of cathepsin S protein (CatS) and toll-like receptor (TLR) 2 were reduced. TLR play an important role in the innate immune system and several lines of evidence indicate an association with atherosclerosis [8].…”

“…Interestingly, Wu et al [6] showed a reduction of (pro) renin receptor (PRR) in plaques of Aliskiren-treated mice. The PRR has recently been discovered with its intracellular downstream cascade and is particularly expressed in vascular smooth muscle cells of heart and kidney [3].…”

“…In fact, recently there has been some evidence that Aliskiren inhibits tissue RAAS more efficiently due to direct antagonism of the non-proteolitically activated prorenin [3]. Wu and colleagues [6] have only focused on local effects of RAAS, but discrimination between the tissue-specific and the systemic effects of Aliskiren need further evaluation and could help explain the results of clinical outcome studies. Interestingly, in a different study using a model of metabolic syndrome, mice lacking renin expressed a favorable phenotype due to higher energy expenditure and resistance to diet-induced obesity [11].…”