Cathepsin
S
Adipose tissue
released cysteine protease involved in the pathogenesis of atherosclerosis.
Weight loss reduces adipose tissue cathepsin
S and its circulating levels in morbidly obese women
CONTEXT: Human adipose tissue produces several adipokines,
including the newly identified protein cathepsin S (CTSS), a cysteine
protease involved in the pathogenesis of atherosclerosis. Obesity
is characterized by high levels of CTSS in the circulation and
in sc white adipose tissue (scWAT). OBJECTIVE: We investigated
the effect of surgery-induced weight loss on circulating CTSS
and its protein expression in scWAT. DESIGN: Fifty morbidly obese
women before and 3 months after surgery and 10 healthy lean women
were studied. We analyzed the relationships between circulating
CTSS and clinical and biological parameters. Immunohistochemistry
of the CTSS protein variations in scWAT was performed. RESULTS:
Weight loss decreased by 42% (P < 0.0001) the circulating CTSS
levels, which correlated with changes in body weight (P = 0.03).
We observed a significant decrease in CTSS enzymatic activity
by 25% after weight loss (P = 0.001). Adipose tissue CTSS content
was reduced by 30% (P = 0.002) after surgery. The variations in
CTSS expression in scWAT after surgery correlated with changes
in circulating CTSS serum levels (P = 0.03). Most of the correlations
between CTSS and clinical and biological parameters disappeared
after adjustment for body mass index, emphasizing the strong link
between CTSS and corpulence in humans. CONCLUSIONS: Changes in
CTSS scWAT might contribute to serum variations in CTSS during
weight loss. The decrease in CTSS concentrations in the circulation
may contribute to vascular improvement in obese subjects after
weight loss.
Taleb S,
et al. J Clin Endocrinol Metab. 2006 Mar;91(3):1042-7. Epub 2006
Jan 4.
Therapeutic perspectives of adipocytokines
Various adipocyte-secreted factors have been described which profoundly
affect insulin sensitivity and might potentially link obesity,
insulin resistance and cardiovascular disease. Among those, adiponectin,
visfatin and omentin appear as insulin-sensitising adipocytokines,
whereas TNF-alpha, IL-6 and resistin induce insulin resistance.
Moreover, leptin is a fat-derived key regulator of appetite and
energy expenditure. Due to their profound effect on whole-body
glucose and energy metabolism, adipocytokines have attracted interest
as potential new therapeutics for diabetes mellitus and obesity.
The current knowledge on function, regulation and therapeutic
potential of various adipocytokines, as well as their clinical
implications, are discussed in this review.
Kralisch
S, et al. Expert Opin Pharmacother. 2005 Jun;6(6):863-72.
Destabilizing role of cathepsin S in
murine atherosclerotic plaques
OBJECTIVE: Lysosomal proteinases have been implicated in a number
of pathologies associated with extracellular matrix breakdown.
Therefore, we investigated the possibility that the lysosomal
proteinase cathepsin S may be involved in atherosclerotic plaque
destabilization. METHODS AND RESULTS: Atherosclerotic plaques
in the brachiocephalic arteries of fat-fed apolipoprotein E/cathepsin
S double knockout mice had 73% fewer acute plaque ruptures (P=0.026)
and were 46% smaller (P=0.025) than those in age-, strain-,
and sex-matched apolipoprotein E single knockout controls. When
the incidence of acute plaque rupture was normalized for plaque
size, the reduction in the double knockouts was 72% (P=0.039).
The number of buried fibrous layers, indicative of an unstable
plaque phenotype, was reduced by 67% in the double knockouts
(P=0.008). The cysteine proteinase inhibitor, egg white cystatin,
was biotinylated and used as an active-site-directed probe for
cathepsins. Biotinylated cystatin selectively detected cathepsin
S in extracts of human carotid atherosclerotic plaque. Active
cathepsin S was detectable in extracts of human atherosclerotic
plaque but not in nondiseased carotid arteries. Active cathepsins
were especially prominent in macrophages in the shoulder regions
of plaques, areas considered to be vulnerable to rupture. Cathepsin
S protein colocalized with regions of elastin degradation in
human coronary plaques. CONCLUSIONS: These data provide direct
evidence that an endogenous proteinase, cathepsin S, plays an
important role in atherosclerotic plaque destabilization and
rupture.
.
Rodgers KJ, et al.Arterioscler Thromb Vasc
Biol. 2006 Apr;26(4):851-6. Epub 2006 Jan 12.
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