Oxidized LDL but not angiotensin II induces cardiomyocyte hypertrophic responses through the interaction between LOX-1 and AT1 receptors.

It is well known that lectin-like oxidized low-density lipoprotein (ox-LDL) and its receptor LOX-1, angiotensin II (AngII) and its type 1 receptor (AT1-R) play an important role in the development of cardiac hypertrophy. However, the molecular mechanism is not clear. In this study, we found that ox-LDL-induced cardiac hypertrophy was suppressed by inhibition of LOX-1 or AT1-R but not by AngII inhibition. These results suggest that the receptors LOX-1 and AT1-R, rather than AngII, play a key role in the role of ox-LDL. The same results were obtained in mice lacking endogenous AngII and their isolated cardiomyocytes. Ox-LDL but not AngII could induce the binding of LOX-1 and AT1-R; inhibition of LOX-1 or AT1-R but not AngII could abolish the binding of these two receptors. Overexpression of wild type LOX-1 with AT1-R enhanced ox-LDL-induced binding of two receptors and phosphorylation of ERKs, however, transfection of LOX-1 dominant negative mutant (lys266ala / lys267ala) or an AT1-R mutant (glu257ala) not only reduced the binding of two receptors but also inhibited the ERKs phosphorylation. Phosphorylation of ERKs induced by ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by an inhibitor of Gq protein rather than Jak2, Rac1 or RhoA. Genetically, an AT1-R mutant lacking Gq protein coupling ability inhibited ox-LDL induced ERKs phosphorylation. Furthermore, through bimolecular fluorescence complementation analysis, we confirmed that ox-LDL rather than AngII stimulation induced the direct binding of LOX-1 and AT1-R. We conclude that direct binding of LOX-1 and AT1-R and the activation of downstream Gq protein are important mechanisms of ox-LDL-induced cardiomyocyte hypertrophy.

Effectiveness and Approach of Rehabilitation in Patients With Acute Heart Failure: A Review

Acute heart failure is associated with high mortality and frequent rehospitalization, resulting in enormous healthcare costs and declining physical function, activities of daily living, and quality of life. Cardiac rehabilitation has been recommended as one of the nonpharmacologic treatments for patients with heart failure. However, much of the evidence for cardiac rehabilitation interventions reported to date has been limited to chronic heart failure. In recent years, the effectiveness of rehabilitation intervention in patients with acute heart failure has been reported, led by the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial. This review overviews the recent evidence of rehabilitation in patients with acute heart failure.

The use of geographical analysis in assessing the impact of patients' home addresses on their participation in outpatient cardiac rehabilitation: a prospective cohort study

PURPOSE@#Geographical analysis is becoming a powerful tool for evaluating the quality of medical services and acquiring fundamental data for medical decision-making. Using geographical analysis, we evaluated the impact of the distance from patients' homes to the hospital on their participation in outpatient cardiac rehabilitation (OCR).@*METHODS@#All patients hospitalized for percutaneous coronary intervention, coronary artery bypass grafting, valvular surgery, congestive heart failure, and aortic diseases were advised to participate in an OCR program after discharge. Using the dataset of our cohort study of OCR from 2004 to 2015 (n = 9,019), we used geographical analysis to investigate the impact of the distance from patients' homes to hospital on their participation in our OCR program.@*RESULTS@#Patients whose road distance from home to hospital was 0-10 km, 10-20 km, and 20-30 km participated more in OCR than those whose road distance was ≧ 30 km (OR 4.34, 95% CI 3.80-4.96; OR 2.98, 95% CI 2.61-3.40; and OR 1.90, 95% CI 1.61-2.23, respectively). Especially in patients with heart failure, the longer the distance, the lesser the participation rate (P < .001).@*CONCLUSIONS@#Using geographical analysis, we successfully evaluated the factors influencing patients' participation in OCR. This illustrates the importance of using geographical analysis in future epidemiological and clinical studies.@*TRIAL REGISTRATION@#UMIN000028435.

Remote cardiac rehabilitation is a good alternative of outpatient cardiac rehabilitation in the COVID-19 era

BACKGROUND@#In the wake of the coronavirus disease 2019 (COVID-19) pandemic, people need to practice social distancing in order to protect themselves from SARS-CoV-2 infection. In such stressful situations, remote cardiac rehabilitation (CR) might be a viable alternative to the outpatient CR program.@*METHODS@#We prospectively investigated patients hospitalized for heart failure (HF) with a left ventricular ejection fraction of < 50%. As for patients who participated in the remote CR program, telephone support was provided by cardiologists and nurses who specialized in HF every 2 weeks after discharge. The emergency readmission rate within 30 days of discharge was compared among the outpatient CR, remote CR, and non-CR groups, and the EQ-5D score was compared between the outpatient CR and remote CR groups.@*RESULTS@#The participation rate of HF patients in our remote CR program elevated during the COVID-19 pandemic. As observed in the outpatient CR group (n = 69), the emergency readmission rate within 30 days of discharge was lower in the remote CR group (n = 30) than in the non-CR group (n = 137) (P = 0.02). The EQ-5D score was higher in the remote CR group than in the outpatient CR group (P = 0.03) 30 days after discharge.@*CONCLUSIONS@#Remote CR is as effective as outpatient CR for improving the short-term prognosis of patients hospitalized for heart failure post-discharge. This suggests that the remote CR program can be provided as a good alternative to the outpatient CR program.

Novel Concept of a Heart-Gut Axis in the Pathophysiology of Heart Failure

Patients with heart failure (HF) have structural and functional changes of the gut as a result of microcirculatory disturbances. A disrupted gut epithelial barrier may lead to translocation of microbial products into systemic circulation, possibly aggravating HF by inducing inflammatory responses. Gut microbiota play an essential role in the maintenance of host homeostasis because large quantities of their gene products complement host physiological processes. Emerging evidence has suggested the potential clinical significance of gut microbiota in the pathophysiology of HF. Imbalances of gut microbe-derived metabolites can contribute to cardiac dysfunction and other morbidities in patients with HF. Therapeutic research for HF through targeting microbiota is under way. Thus, the novel concept of a heart-gut axis may lead to breakthroughs in the development of innovative diagnostics and therapeutic approaches for HF.

Cardiac Rehabilitation Increases Exercise Capacity with a Reduction of Oxidative Stress

BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) mediate various signaling pathways that underlie vascular inflammation in atherogenesis and cardiovascular diseases. Cardiac rehabilitation (CR) has a variety of multiple beneficial effects, including anti-inflammatory effects. The purpose of the present study was to investigate the effects of CR on ROS in patients with cardiovascular diseases. SUBJECTS AND METHODS: The serum level of derivatives of reactive oxidative metabolites, an index of oxidative stress, was measured in 100 patients with cardiovascular diseases before, and, subsequently, 3 and 6 months after, CR. A biological antioxidant potential (BAP) test was applied to assess the antioxidant power of the serum. RESULTS: The resting reactive oxidative metabolite levels decreased 3-6 months after CR {pre: 351+/-97 Carratelli unit (CARR U), 3 months: 329+/-77 CARR U, 6 months: 325+/-63 CARR U, all p<0.01} with the increase of the percentage of the predicted values of VO2 peak and the percentage of the predicted values of VO2 at the anaerobic threshold (VO2 AT) and the decrease of the B-type natriuretic peptide (BNP). The BAP test and antioxidative/oxidative stress ratio increased 6 months after CR. The % changes of the antioxidative/oxidative stress ratio was positively correlated with the % changes of VO2 AT, and negatively correlated with the % changes of the BNP. CONCLUSION: These results suggest that intensive supervised CR significantly improved exercise capacity, which may be attributable to an adaptive response involving more efficient oxidative metabolites or the increased capacity of endogenous anti-oxidative systems in patients with cardiovascular diseases.