Identification of potential crucial cuproptosis-related genes in myocardial ischemia-reperfusion injury through the bioinformatic analysis.

BACKGROUND: Cuproptosis is known to regulate diverse physiological functions in many diseases, but its role in regulating Myocardial Ischemia-Reperfusion Injury (MI/RI) remains unclear. METHODS: For this purpose, the MI/RI microarray datasets GSE61592 were downloaded from the Gene Expression Omnibus (GEO) database, and the Differently Expressed Genes (DEGs) in MI/RI were identified using R software. Moreover, the MI/RI mice model was established to confirm further the diagnostic value of Pyruvate Dehydrogenase B (Pdhb), Dihydrolipoamide S-acetyltransferase (Dlat), and Pyruvate dehydrogenase E1 subunit alpha 1 (Pdhα1). RESULTS: The analysis of microarray datasets GSE61592 revealed that 798 genes were upregulated and 768 were downregulated in the myocardial tissue of the ischemia-reperfusion injury mice. Furthermore, Dlat, Pdhb, Pdhα1, and cuproptosis-related genes belonged to the downregulated genes. The receiver operating characteristics curve analysis results indicated that the Dlat, Pdhb, and Pdhα1 levels were downregulated in MI/RI and were found to be potential biomarkers for MI/RI diagnosis and prognosis. Similarly, analysis of Dlat, Pdhb, and Pdhα1 levels in the MI/RI mice revealed Pdhb being the key diagnostic marker. CONCLUSIONS: This study demonstrated the prognostic value of cuproptosis-related genes (Dlat, Pdhb, and Pdhα1), especially Pdhb, MI/RI, providing new insight into the MI/RI treatment.

Sex Differences in Murray Law-Based Quantitative Flow Ratio Among Patients With Intermediate Coronary Lesions.

Background The Murray law-based quantitative flow ratio (µQFR) is a novel technique that simulates fractional flow reserve (FFR) from a single angiographic view. However, the impact of sex differences on the diagnostic performance of µQFR has not been investigated. Methods and Results In this study, FFR and µQFR were assessed in 497 intermediate stenoses (30%-70% by visual estimation) from 460 patients (34.3% female). Physiological significance was defined as FFR ≤0.80 or µQFR ≤0.80. After adjusting for potential confounders, female sex was independently associated with higher FFR (P=0.048 and 0.026, respectively) and µQFR (P=0.001 for both) in both fully adjusted and stepwise backward models. µQFR provided superior diagnostic accuracy compared with angiography alone for detecting FFR ≤0.80 in both women (area under the curve, 0.93 [95% CI, 0.88-0.97] versus 0.80 [95% CI, 0.73-0.86]; P=0.001) and men (area under the curve, 0.88 [95% CI, 0.84-0.92] versus 0.73 [95% CI, 0.68-0.78]; P<0.001), with comparable performance between the sexes (P=0.175). In the multivariable analysis, sex was not a significant factor contributing to the overall disagreement between FFR and µQFR. Conclusions Regardless of angiographic stenosis severity, women tend to have higher FFR and µQFR values than men. Furthermore, µQFR performs similarly well in both sexes and offers improved diagnostic accuracy over angiography alone, indicating its potential as a reliable, wire-free tool to identify functional ischemia.

Inhibition of miR-195-3p protects against cardiac dysfunction and fibrosis after myocardial infarction.

Cardiac fibrosis following myocardial infarction is a major risk factor for heart failure. Recent evidence suggests that miR-195-3p is up-regulated in fibrotic diseases, including kidney and liver fibrosis. However, its function and underlying mechanisms in cardiac fibrosis after MI remain unknown. To investigate the role of miR-195-3p in MI-induced cardiac fibrosis, we established acute MI models by ligating adult C57B/L6 mice LAD coronary artery while sham-operated mice were used as controls. In vivo inhibition of miR-195-3p was conducted by intramyocardial injection of AAV9-anti-miR-195-3p. In vitro overexpression and inhibition of miR-195-3p were performed by transfecting cultured Cardiac Fibroblasts (CFs) with synthetic miRNA mimic and inhibitor. Our results showed that MI induced the expression of miR-195-3p and that inhibition of miR-195-3p reduced myofibroblast differentiation and collagen deposition and protected cardiac function. In vitro stimulation of CFs with TGF-ß1 resulted in a significant increase in miR-195-3p expression. Inhibition of miR-195-3p attenuated the TGF-ß1-induced expression of ECM proteins, migration, and proliferation. PTEN expression was significantly reduced in the hearts of MI mice, in activated CFs, and in CFs transfected with miR-195-3p mimic. Inhibition of miR-195-3p markedly restored PTEN expression in MI mice and TGF-ß1-treated CFs. In conclusion, this study highlights the crucial role of miR-195-3p in promoting cardiac fibrosis and dysfunction after MI. Inhibiting miR-195-3p could be a promising therapeutic strategy for preventing cardiac fibrosis and preserving cardiac function after MI. Additionally, the study sheds light on the mechanisms underlying the effects of miR-195-3p on fibrosis, including its regulation of PTEN/AKT pathway.

Association between dietary intake of anthocyanidins and heart failure among American adults: NHANES (2007-2010 and 2017-2018).

Background: Despite anthocyanidins have anti-inflammatory and antioxidant properties, no studies have researched association between dietary intake of anthocyanidins and heart failure. Methods: We enrolled 15,869 participants from the National Health and Nutrition Examination Survey (NHANES) (2007-2010 and 2017-2018) in this cross-sectional study. We examined baseline data and prevalence of heart failure in different quartile groups of anthocyanin intake (Q1-4). Three models were established through logistic regression to evaluate the protective effect of Q4 (highest anthocyanidins intake) on heart failure. The protective effect of high anthocyanidins intake on heart failure was further evaluated in different subgroups. Results: Participants with the highest anthocyanidins intake (Q4) had the lowest prevalence of heart failure (Q1:2.54%, Q2:2.33%, Q3:2.43%, Q4:1.57%, p = 0.02). After adjusting for possible confounding factors, compared with the Q1 group, the highest anthocyanidins intake (Q4) was independently related to lower presence of heart failure (Q4: OR 0.469, 95%CI [0.289, 0.732], p = 0.003). And this association was still stable in subgroups of female, ≥45 years, smoker, non-Hispanic White or without diabetes, stroke and renal failure. Conclusion: Dietary intake of anthocyanidins had negative association with the presence of heart failure.

Albumin to globulin ratio was associated with in-stent restenosis and revascularization events after percutaneous coronary intervention.

In-stent restenosis is a common complication after percutaneous coronary intervention (PCI) for coronary heart disease requiring revascularization. We performed a retrospective analysis to assess the value of inflammatory biomarker albumin to globulin ratio (AGR) in clinical prognosis of PCI. In total, 992 patients with coronary heart disease who underwent the first drug-eluting stent implantation and re-examination angiography in our hospital were enrolled in this study. The AGR was measured. At mean follow-up of 11.2 ± 4 months, the in-stent restenosis (ISR) and revascularization events (including target lesion revascularization, target vessel revascularization, and revascularization of de novo lesions) occurred in 127 and 284 patients, respectively. Compared with the non-ISR or non-event group, AGR was significantly lower in the ISR group and the events group. Beyond that, albumin was significantly lower, whereas urea nitrogen, glucose, and Gensini score, as well as the proportions of a history of diabetes and peripheral vascular diseases were significantly higher in the ISR group and the events group. Age, heart rate, white blood cell, neutrophils, lymphocyte, monocyte, and incidence of ischemic stroke were significantly higher in the events group. Multivariate Cox regression analysis showed that AGR was independently associated with ISR (p = 0.032) and events (p = 0.024). Besides, Kaplan-Meier analysis indicated that the higher quartile of AGR had a lower rate of ISR (p = 0.038) and events (p ≤ 0.001). Finally, the receiver operating characteristic curve for AGR in diagnosing ISR and events indicated that the area under the curve were 0.56 and 0.57, respectively. Therefore, AGR is one of the most important factors that independently associate with the ISR and revascularization events after PCI.

Clinical prediction models of fractional flow reserve: an exploration of the current evidence and appraisal of model performance.

BACKGROUND: Invasive fractional flow reserve (FFR) is a standard indicator of coronary stenoses' hemodynamic severity. Clinical prediction models (CPMs) may help differentiate ischemic from non-ischemic lesions without using a pressure wire but by integrating related variables. This approach differs from that of physics-based models. However, it is not yet known which CPMs are the most reliable at detecting hemodynamic significance. METHODS: A systematic review was performed of relevant publications that developed or validated any FFR CPMs from inception to April 2019 in the PubMed, EMBASE, and Cochrane Library databases by two independent authors. The risk of bias and applicability were assessed using the prediction model risk of the bias assessment tool (PROBAST). RESULTS: A total of 11 unique CPMs and 5 subsequent external validation studies were identified. The prevalence of hemodynamically significant lesions (FFR ≤0.80) across the studies had a median of 37.1% (range: 20.7-68.0%). Lesion length, percent diameter stenosis, and minimal lumen diameter were the three most frequently used variables in the CPMs. Of the 11 FFR CPMs, 9 (82%) exhibited strong discrimination [area under the curve (AUC) >0.75], and 5 (45%) had been subject to external validation; however, calibration was only available for 3 models (27%). There was a high degree of applicability; however, none of the studies was assessed as having a low risk of bias. A CPM was identified that had undergone rigorous validation and calibration: the DILEMMA score (three validations; median AUC, 0.83). CONCLUSIONS: Almost half of the existing FFR CPMs had been externally validated. Due to their good discrimination abilities, these FFR CPMs are useful tools that could reduce the need for invasive hemodynamic measurements. Future research that adheres to methodological guidelines should be undertaken to develop high-quality models in this setting. (PROSPERO registration number: CRD42019125011).

Impact of diabetes mellitus on the relationship between a Poiseuille-based index and fractional flow reserve in intermediate coronary lesions.

BACKGROUND: The ratio of lesion length (LL) to the fourth power of minimal lumen diameter (MLD) (LL/MLD4) is a Poiseuille-based index with good diagnostic accuracy for the detection of coronary lesions with abnormal fractional flow reserve (FFR). We aimed to evaluate the impact of diabetes mellitus (DM) on its performance in intermediate coronary stenoses. METHODS: We performed quantitative coronary angiography and simultaneous FFR measurement in 324 patients (234 non-DM and 90 DM) with 335 coronary lesions. The area under the receiver-operating characteristic curve (AUC) for angiographic parameters was determined, using an FFR value ≤0.80 to indicate the physiological significance of coronary stenoses. RESULTS: In the non-DM group, FFR was significantly related to percent diameter stenosis (%DS) (R = -0.238) and LL/MLD4 ratio (R = -0.301; P < 0.001 for both). In the DM group, there was no correlation between %DS and FFR, whereas a close-to-threshold correlation was observed for the LL/MLD4 ratio (R = -0.205; P = 0.048). The AUC of LL/MLD4 ratio was significantly different between non-diabetic and diabetic subjects (0.738 vs. 0.540; P = 0.024). Moreover, the LL/MLD4 ratio showed higher AUCs than %DS (0.738 vs. 0.635; P = 0.017) and LL (0.738 vs. 0.634; P = 0.024) in non-diabetic population but this superiority did not exist in diabetic population. CONCLUSION: We showed good diagnostic accuracy of LL/MLD4 ratio for identifying ischemic lesions in patients without DM. However, there was an impaired performance in diabetic patients and thus FFR measurement is essential to determine their hemodynamic status.