BackgroundMetabolic risk factors and abnormalities such as obesity and hypertension are rapidly rising among the Chinese population following China’s tremendous economic growth and widespread westernization of lifestyle in recent decades. Limited information is available about the current burden of metabolic syndrome (MetS) in China.MethodsWe analyzed data on metabolic risk factors among 22,457 adults aged ≥ 32 years participating in the “Zhabei Health 2020” survey (2009–2010), a cross-sectional study of a representative sample of community residents in Zhabei District. We defined MetS using Chinese-specific cut-off points for central obesity according to consensus criteria recently endorsed by several international and national organizations in defining MetS in different populations worldwide. We used a multiple logistic regression model to assess the associations of potential risk factors with MetS.ResultsThe unadjusted prevalence of the MetS was 35.1% for men and 32.5% for women according to the consensus criteria for Chinese. The prevalence increased progressively from 12.1% among participants aged 32–45 years to 45.4% among those aged ≥ 75 years. Age, smoking, family history of diabetes, and education are significantly associated with risk of MetS.ConclusionsThe MetS is highly prevalent and has reached epidemic proportion in Chinese urban adult community residents.
Background
Pharmacologic activation of cGMP-dependent protein kinase I (PKGI) has emerged as a therapeutic strategy for humans with heart failure. However, PKG activating drugs have been limited by hypotension arising from PKG-induced vasodilation. PKGIα anti-remodeling substrates specific to the myocardium might provide targets to circumvent this limitation, but currently remain poorly understood.
Methods and Results
We performed a screen for myocardial proteins interacting with the PKGIα leucine zipper (LZ) binding domain to identify myocardial-specific PKGI anti-remodeling substrates. Our screen identified cardiac myosin binding protein C (cMyBP-C), a cardiac myocyte-specific protein, which has been demonstrated to inhibit cardiac remodeling in the phosphorylated state, and when mutated leads to hypertrophic cardiomyopathy in humans. GST-pulldowns and precipitations with cGMP-conjugated beads confirmed the PKGIα-cMyBP-C interaction in myocardial lysates. In vitro studies demonstrated that purified PKGIα phosphorylates the cMyBP-C M-domain at Ser-273, Ser-282, and Ser-302. cGMP induced cMyBP-C phosphorylation at these residues in COS cells transfected with PKGIα, but not in cells transfected with LZ mutant PKGIα containing mutations to disrupt LZ substrate binding. In mice subjected to LV pressure overload, PKGI activation with sildenafil increased cMyBP-C phosphorylation at Ser-273 compared with untreated mice. cGMP also induced cMyBP-C phosphorylation in isolated cardiac myocytes.
Conclusions
Taken together these data support that PKGIα and cMyBP-C interact in the heart, and that cMyBP-C is an anti-remodeling PKGIα kinase substrate. This study provides the first identification of a myocardial specific PKGIα LZ-dependent anti-remodeling substrate and supports further exploration of PKGIα myocardial LZ substrates as potential therapeutic targets for heart failure.
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