Less may be more: Using small molecules to reprogram human cells into functional cardiomyocytes.

The prospect of genetically reprogramming cardiac fibroblasts into induced cardiomyocytes by using cardio-differentiating transcription factors represents a significant advantage over previous strategies involving stem cell implantation or the delivery of angiogenic factors. Remarkably, intramyocardial administration of cardio-differentiating factors consistently results in 20% to 30% improvements in postinfarct ejection fraction and nearly a 50% reduction in myocardial fibrosis in murine models. Despite these encouraging observations, few breakthroughs have been made in the reprogramming of human cells, which have more rigorous epigenetic constraints and gene regulatory networks that oppose reprogramming. As a potential solution to this challenge, Cao and colleagues used a cocktail of 9 chemicals capable of reprogramming human fibroblasts into contractile cardiomyocyte-like cells, albeit at a low efficiency. This strategy would obviate the concerns with viral vectors and appears to partially overcome the epigenetic constraints in human cells. Nevertheless, significant challenges, including drug-drug interactions, low reprogramming efficiency, and lack of in vivo data must be overcome before future clinical application.

Short-term and long-term cardiovascular risk, metabolic syndrome and HIV in Tanzania.

OBJECTIVE: To compare short-term and long-term cardiovascular disease (CVD) risk scores and prevalence of metabolic syndrome in HIV-infected adults receiving and not receiving antiretroviral therapy (ART) to HIV-negative controls. METHODS: A cross-sectional study including 151 HIV-infected, ART-naive, 150 HIV-infected on ART and 153 HIV-negative adults. Traditional cardiovascular risk factors were determined by standard investigations. The primary outcome was American College of Cardiology/American Heart Association Atherosclerotic CVD (ASCVD) Risk Estimator lifetime CVD risk score. Secondary outcomes were ASCVD 10-year risk, Framingham risk scores, statin indication and metabolic syndrome. RESULTS: Compared with HIV-negative controls, more HIV-infected adults on ART were classified as high lifetime CVD risk (34.7% vs 17.0%, p<0.001) although 10-year risk scores were similar, a trend which was similar across multiple CVD risk models. In addition, HIV-infected adults on ART had a higher prevalence of metabolic syndrome versus HIV-negative controls (21.3% vs 7.8%, p=0.008), with two common clusters of risk factors. More than one-quarter (28.7%) of HIV-infected Tanzanian adults on ART meet criteria for statin initiation. CONCLUSIONS: HIV-infected ART-treated individuals have high lifetime cardiovascular risk, and this risk seems to develop rapidly in the first 3-4 years of ART as does the development of clusters of metabolic syndrome criteria. These data identify a new subgroup of low short-term/high-lifetime risk HIV-infected individuals on ART who do not currently meet criteria for CVD risk factor modification but require further study.