Recent studies have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors play a beneficial role for normoglycemic patients with heart failure (HF). However, the underlying mechanism remains largely unexplored. In the present study, we aimed to investigate the cardioprotective effect of SGLT2 inhibitors in a normoglycemic rabbit model of chronic heart failure (CHF) and its potential mechanism was also explored. A total of 24 male New Zealand white rabbits were randomly divided into the sham group, HF group, perindopril group, and dapagliflozin (DAPA) group. The normoglycemic CHF model was established by aortic constriction for 12 weeks. In the 13th week, DAPA (1 mg/kg/day) or perindopril (0.5 mg/kg/day) was administered by oral gavage daily for 10 weeks. Both the sham group and HF group were given normal saline via gavage. After 10 weeks, the heart structure and function were evaluated by echocardiography and plasma NT-proBNP. Moreover, cardiac fibrosis was analyzed using immunohistochemistry, Masson’s trichrome staining, and Western blotting analysis. The results showed that DAPA improved the myocardial structure and function of normoglycemic CHF rabbits and ameliorated myocardial fibrosis. Further study indicated that DAPA suppressed cardiac fibrosis by inhibiting the transforming growth factor β1 (TGF-β1)/Smad signaling pathway. Collectively, our findings showed that DAPA could ameliorate cardiac fibrosis in normoglycemic CHF rabbits by inhibiting the TGF-β1/Smad signaling pathway.
The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL) and to elucidate its possible mechanism. Cell Counting Kit-8 assay was used to detect cell viability. Reverse transcription-quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL-1β, IL-6 and TNF-α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, endothelin-1, caspase-3, Bax, Bcl-2, Toll-like receptor 4 (TLR4), p65 and p-p65. Compared with the ox-LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl-2 expression, decreased the levels of IL-1β, IL-6 and TNF-α and reduced the expressions of MALAT1, ICAM-1, VCAM-1, cleaved-caspase-3, Bax, TLR4 and p-p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox-LDL-induced HUVECs via inactivating the TLR4/NF-κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.
Takayasu arteritis (TA) is now recognized worldwide and is a disease that mainly affects the aorta and its main branches. TA rarely involves the small or medium-sized vessels. Certain vascular lesions, such as arterial stenosis, occlusion, and aneurysm are common with TA. However, patients with new-onset TA who present with left main trunk acute non-ST segment elevation myocardial infarction are extremely rare. We report a 16-year-old female patient with non-ST segment elevation myocardial infarction due to severe stenosis of the left main coronary artery that was caused by TA. She was eventually diagnosed with TA and underwent successful coronary artery stenting combined with glucocorticoids and folate reductase inhibitor therapy. Over the 1-year follow-up, she experienced two episodes of chest pain and was admitted to the hospital. During the second hospitalization, coronary angiography (CAG) revealed 90% stenosis of the original left main trunk (LM) stent. Following percutaneous coronary angiography (PTCA), drug-coated balloon (DCB) angioplasty was performed. Fortunately, a clear diagnosis of TA was made, and treatment was initiated with an interleukin-6 (IL-6) receptor inhibitor. Early diagnosis and therapy for TA are emphasized.
<b><i>Background:</i></b> The association between a patent foramen ovale (PFO) and cryptogenic stroke (CS) is well established, and the benefits of PFO closure are clearly recognized. This study aimed to investigate the presence of a residual shunt in patients who have experienced cryptogenic cerebrovascular events following a PFO closure. <b><i>Methods:</i></b> Two researchers systematically searched the PubMed and Embase online database for pertinent clinical studies published between January 2000 and July 2021 concerning the recurrence of cerebrovascular events after PFO closures. <b><i>Results:</i></b> Upon screening an initial list of 2,342 articles, six studies were identified, involving 2,083 patients. Overall, the analysis indicated a marked difference in the recurrence of cerebrovascular events in 8.89% of residual shunt (RS) cases compared to only 2.90% of non-RS cases. The summary odds ratio was 3.484 (95% confidence interval, 2.169–5.596), which suggested that RS may be a risk factor for recurrent cerebrovascular events in patients that experienced PFO-related cerebrovascular events within 6 months after PFO closure surgery. <b><i>Conclusions:</i></b> The presence of RS significantly increases the risk of recurrent cerebrovascular events in patients with clinical PFO closure.
Background To investigate the predictive value of low-density lipoprotein cholesterol (LDL-C), total stent length and number of implanted stents in patients with unstable angina (UA) regarding myocardial injury and infarction during perioperative period. Methods Three hundred and fifteen consecutive UA patients between January 2015 and June 2018 were retrospectively recruited from two cardiac centers of Hebei Province, China. These patients had normal preprocedural cardiac troponin I (cTnI) and underwent uneventful revascularizations. The predictive value of baseline LDL-C level and total stent length was investigated by linking to post procedural cTnI value in this cohort. Meanwhile, other related clinical and procedural variables were analyzed. Results Baseline LDL-C level or LDL-C grade was correlated with post percutaneous coronary intervention (PCI) cTnI levels (r = 0.120, P = 0.01; r = 0.157, P = 0.004). LDL-C grade was an independent risk factor of perioperative myocardial injury and infarction (P < 0.05) after multivariable adjustment. The risk increased with the elevation of baseline LDL-C level. Compared to the lowest level group (<70 mg/dl), the group with 70–99 mg/dl carried three times higher risk (OR = 3.318; 95% CI: 1.167–9.436; P < 0.05). And, patients with LDL-C level ≥100 mg/dl had the worst prognosis (OR = 4.783; 95% CI: 1.736–13.180; P = 0.002). Besides, the study also found that the total length of stent was predictive of perioperative myocardial injury and infarction independently (OR = 1.037; 95% CI: 1.017–1.058; P = 0.001). Conclusion Baseline LDL-C level and total stent length were independent predictors of periprocedural myocardial injury and infarction in UA patients undergoing elective PCI.
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