Atorvastatin May Delay Cardiac Aging by Upregulating Peroxisome Proliferator-Activated Receptors in Rats

Abstract

Aims: To investigate the effect of atorvastatin on cardiac aging in rats. Materials: Ninety 20-month-old Wistar rats were administered oral atorvastatin (AVT; 10 or 1 mg·kg^-1·day^-1) or saline for 4 months. At the end of the experiment, age-related changes in hearts were measured. Results: Compared with young rats, obvious increases were found in the aging rats in left ventricle thickness, diameter of cardiocytes, collagen deposition, the ratio of type I/type III collagen, β-galactosidase and malondialdehyde (MDA), and obvious decreases were found in superoxide dismutase (SOD), catalase (CAT) and nitric oxide synthase (NOS). The treatment with AVT led to significant decreases in the thickness of the left ventricle, diameter of cardiocytes, collagen deposition, I/III collagen ratio, MDA, β-galactosidase and increases in the activity of SOD, CAT and NOS. Some aging-related inflammatory cytokines like interleukin (IL)-1β, tumour necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 were found to be overexpressed in the aging rats. AVT treatment could inhibit the expression of IL-1β, TNF-α and MMP-9 on both the mRNA and protein levels, and increase the expression of peroxisome proliferator-activated receptors (PPAR-α/β/δ/γ). Pretreatment with PPAR inhibitors attenuated the inhibitory effect of AVT on the expression of inflammatory cytokines. Conclusion: AVT may retard the cardiac aging process by upregulating PPARs.

The effects of additional ezetimibe treatment to baseline rosuvastatin on circulating PCSK9 among patients with stable angina

“…This plateau effect has also been confirmed by many other investigators when compared between different doses of statins (16). Besides the mechanism mentioned above, statins may upregulate PCSK9 concentrations by peroxisome proliferator-activated receptor (PPAR) related pathway (21,22) or sterol regulatory element binding protein-2 (SREBP-2) associated mechanism (7,(23)(24)(25). However, ezetimibe has not been discovered with such pleiotropic effects.…”

Effects of age and caloric restriction on the cardiac and coronary response to endothelin-1 in rats

“…In the present study although the gene expression of some inflammatory markers such as COX-2, IL-6, or IL-1β was not modified in response to aging, we found an overexpression of iNOS and TNF-α in the heart of 24-month-old rats. Likewise the expression of these factors have been found to be increased both in the heart (Han et al, 2012) and in coronary arteries (Csiszar et al, 2002(Csiszar et al, , 2003 restriction for three months did not prevent aging-induced increase of iNOS and TNF-α. The same protocol of caloric restriction did not prevent aging-induced changes in the expression of TNF-α in other tissues such as the liver or the adipose tissue (Horrillo et al, 2011), which could be explained by either the small reduction in caloric intake (20%) or by the short duration of caloric restriction (3 months).…”

Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

“…Metabolomic analysis indicated an age-dependent decrease in cardiac glucose content, signs of decreased ketone supply, and altered FA synthesis (62). The importance of PPARα inhibition in accelerating cardiac aging was demonstrated in 20-month-old rats that were treated with the lipid lowering drug atorvastatin, which increases PPARα expression (63). The treatment with atorvastatin reduced cardiac hypertrophy, collagen deposition, oxidative stress, expression of inflammatory cytokines, and the aging marker β-galactosidase.…”

“…The treatment with atorvastatin reduced cardiac hypertrophy, collagen deposition, oxidative stress, expression of inflammatory cytokines, and the aging marker β-galactosidase. The conclusion about the association of PPARα inhibition and cardiac aging was further emphasized when pretreatment with PPAR inhibitors attenuated the effect of atorvastatin on the inhibition of inflammatory cytokines (63). This indicated that the beneficial effects of atorvastatin on cardiac aging may be attributed to either lipid lowering effect or the anti-inflammatory role of PPAR signaling (64,65).…”