Elevated ITGA1 levels in type 2 diabetes: implications for cardiac function impairment.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies. METHODS: Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals' left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF. RESULTS: Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF. CONCLUSIONS/INTERPRETATION: ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes. DATA AVAILABILITY: The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org .

miR-455-5p promotes pathological cardiac remodeling via suppression of PRMT1-mediated Notch signaling pathway.

Pathological cardiac remodeling plays an essential role in the progression of cardiovascular diseases, and numerous microRNAs have been reported to participate in pathological cardiac remodeling. However, the potential role of microRNA-455-5p (miR-455-5p) in this process remains to be elucidated. In the present study, we focused on clarifying the function and searching the direct target of miR-455-5p, as well as exploring its underlying mechanisms in pathological cardiac remodeling. We found that overexpression of miR-455-5p by transfection of miR-455-5p mimic in vitro or tail vain injection of miR-455-5p agomir in vivo provoked cardiac remodeling, whereas genetic knockdown of miR-455-5p attenuated the isoprenaline-induced cardiac remodeling. Besides, miR-455-5p directly targeted to 3'-untranslated region of protein arginine methyltransferase 1 (PRMT1) and subsequently downregulated PRMT1 level. Furthermore, we found that PRMT1 protected against cardiac hypertrophy and fibrosis in vitro. Mechanistically, miR-455-5p induced cardiac remodeling by downregulating PRMT1-induced asymmetric di-methylation on R1748, R1750, R1751 and R1752 of Notch1, resulting in suppression of recruitment of Presenilin, Notch1 cleavage, NICD releasing and Notch signaling pathway. Finally, circulating miR-455-5p was positively correlated with parameters of left ventricular wall thickening. Taken together, miR-455-5p plays a provocative role in cardiac remodeling via inactivation of the PRMT1-mediated Notch signaling pathway, suggesting miR-455-5p/PRMT1/Notch1 signaling axis as potential therapeutic targets for pathological cardiac remodeling.

Habitual physical activity improves outcomes among patients with myocardial infarction.

Purpose: This study evaluates the association between habitual physical activity (HPA) and the outcomes of patients with myocardial infarction (MI). Methods: Patients newly diagnosed with MI were divided into two groups based on whether they engaged in HPA, defined as an aerobic activity with a duration of no less than 150 min/week, before the index admission. The primary outcomes included major adverse cardiovascular events (MACEs), cardiovascular (CV) mortality, and cardiac readmission rate 1 year following the index date of admission. A binary logistic regression model was applied to analyze whether HPA was independently associated with 1-year MACEs, 1-year CV mortality, and 1-year cardiac readmission rate. Results: Among the 1,266 patients (mean age 63.4 years, 72% male), 571 (45%) engaged in HPA, and 695 (55%) did not engage in HPA before MI. Patients who participated in HPA were independently associated with a lower Killip class upon admission (OR = 0.48: 95% CI, 0.32-0.71, p < 0.001) and a lower prevalence of 1-year MACEs (OR = 0.74: 95% CI, 0.56-0.98, p = 0.038) and 1-year CV mortality (OR = 0.50: 95% CI, 0.28-0.88, p = 0.017) than those who did not participate in HPA. HPA was not associated with cardiac-related readmission (OR = 0.87: 95% CI, 0.64-1.17, p = 0.35). Conclusions: HPA before MI was independently associated with a lower Killip class upon admission, 1-year MACEs, and 1-year CV mortality rate.

Prognostic value of the combination of neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and platelet-to-lymphocyte ratio on mortality in patients on maintenance hemodialysis.

BACKGROUND: Hemodialysis (HD) is the most important renal replacement therapy for patients with end-stage kidney disease (ESKD). Systemic inflammation is a risk factor of mortality in HD patients. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are new inflammatory markers. However, previous studies have inconsistent conclusions about the predictive value of NLR, MLR and PLR on mortality of HD patients. The aim of this study was to establish an inflammation scoring system by including NLR, MLR and PLR, and evaluate the association between the inflammation score and all-cause and cardiovascular mortality in HD patients. METHODS: In this single center retrospective cohort study, 213 incident HD patients from January 1, 2015 to December 31, 2020 were included. Baseline demographic and clinical data and laboratory measurements were collected. According to the optimal cut-off values, NLR, MLR and PLR were assigned 0 or 1 point, respectively. Then, the inflammation score was obtained by adding the NLR, MLR and PLR scores. All patients were followed until July 31, 2021. The associations of the inflammation score with all-cause and cardiovascular mortality were assessed by multivariable-adjusted Cox models. RESULTS: Of 213 patients, the mean (± SD) age was 56.8 ± 14.4 years, 66.2% were men, and 32.9% with diabetes. The primary cause of ESKD was mainly chronic glomerulonephritis (46.5%) and diabetic nephropathy (28.6%). The median inflammation score was 2 (interquartile range = 1-3). During a median 30 months (interquartile range = 17-50 months) follow-up period, 53 patients had died, of which 33 deaths were caused by cardiovascular disease. After adjusting for demographics, primary diseases and other confounders in multivariable model, the inflammation score = 3 was associated with a hazard ratio for all-cause mortality of 4.562 (95% confidence interval, 1.342-15.504, P = 0.015) and a hazard ratio for cardiovascular mortality of 4.027 (95% confidence interval, 0.882-18.384, P = 0.072). CONCLUSION: In conclusion, an inflammation scoring system was established by including NLR, MLR and PLR, and the higher inflammation score was independently associated with all-cause mortality in HD patients.