Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b.

The activation of the renin-angiotensin system (RAS) induced by increased angiotensin II (AngII) levels has been implicated in muscle atrophy, which is involved in the pathogenesis of congestive heart failure. Although peroxisome proliferator-activated receptor gamma (PPARγ) activation can suppress RAS, the exact role of PPARγ in AngII-induced muscle atrophy is unclear. Here we identified PPARγ as a negative regulator of miR-29b, a microRNA that is able to promote multiple types of muscle atrophy. Suppression of miR-29b could prevent AngII-induced muscle atrophy both in vitro and in vivo. IGF1, PI3K(p85α), and Yin Yang 1 (YY1) were identified as target genes of miR-29b, and overexpression of these targets could rescue AngII-induced muscle atrophy. Importantly, inhibition of PPARγ was sufficient to induce muscle atrophy, while PPARγ overexpression could attenuate that. These data indicate that the PPARγ/miR-29b axis mediates AngII-induced muscle atrophy, and increasing PPARγ or inhibiting miR-29b represents a promising approach to counteract AngII-induced muscle atrophy.

miR-29b contributes to multiple types of muscle atrophy.

A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.

Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice.

In a multicenter randomized double-blind study we demonstrated that Qiliqiangxin (QLQX), a traditional Chinese medicine, had a protective effect in heart failure patients. However, whether and via which mechanism QLQX attenuates cardiac remodeling after acute myocardial infarction (AMI) is still unclear. AMI was created by ligating the left anterior descending coronary artery in mice. Treating the mice in the initial 3 days after AMI with QLQX did not change infarct size. However, QLQX treatment ameliorated adverse cardiac remodeling 3 weeks after AMI including better preservation of cardiac function, decreased apoptosis and reduced fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) was down-regulated in control animals after AMI and up-regulated by QLQX administration. Interestingly, expression of AKT, SAPK/JNK, and ERK was not altered by QLQX treatment. Inhibition of PPARγ reduced the beneficial effects of QLQX in AMI remodeling, whereas activation of PPARγ failed to provide additional improvement in the presence of QLQX, suggesting a key role for PPARγ in the effects of QLQX during cardiac remodeling after AMI. This study indicates that QLQX attenuates cardiac remodeling after AMI by increasing PPARγ levels. Taken together, QLQX warrants further investigation as as a therapeutic intervention to mitigate remodeling and heart failure after AMI.