Journal of Cardiovascular Pharmacology and Therapeutics最新文献

The present study aimed to evaluate the effects of curcumin on the percentage of Tregs as well as miR-21 gene expression and IL-6 levels in peripheral blood mononuclear cells (PBMCs) in patients experiencing myocardial infarction (MI) compared to the controls. Isolation of PBMCs was performed from the peripheral blood of the subjects of the studied groups (50 patients with MI as a case group, and 50 controls). The effects of the low doses of curcumin (0.1 and 1 µM, for 48 h) on the studied parameters were evaluated and compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells. For gene expression measurement and cytokines assay, Real-time PCR and ELISA were carried out. The proportion of regulatory T cells was markedly lower in PBMCs from patients with MI (P = .03) compared to the controls. microRNA (miR)-21 expression (P = .01) was decreased while the serum level of IL-6 was increased (P = .008) in PBMCs from patients with MI compared to the controls. In vitro, curcumin treatment improved the percentage of Tregs (P =.02) while decreasing miR-21 expression (0.03) and the IL-6 level (P = .02) in PBMCs isolated from patients with MI when compared to untreated cells. The present study provided new insights into the mechanism of the anti-inflammatory effect of curcumin by affecting miR-21/Tregs in MI. Therefore, curcumin may be effective in the improvement of cardiac injury after MI through immunomodulatory mechanisms.

Microgravity conditions cause myocardial atrophy and dysfunction with limited therapeutics. Accumulating evidence demonstrates that the deficiency of nicotinamide adenine dinucleotide (NAD⁺) contributes to myocardial dysfunction under microgravity, making NAD⁺ boosting an appealing therapeutic approach. In this study, we sought to investigate whether β-nicotinamide mononucleotide (NMN), a precursor of NAD⁺, preserved cardiomyocytes size and myocardial function during microgravity. Simulated microgravity was induced by tail-suspension in C57BL/6 mice for 28 days. NMN (100 mg/kg body weight) was given every other day after the onset of tail-suspension. Tail-suspension reduced the NAD⁺ content in hearts and decreased the heart weight and cardiomyocytes size, and cardiac function. Administration of NMN attenuates myocardial atrophy and preserves myocardial function in tail-suspended mice. These cardioprotective effects of NAD⁺ repletion were associated with the reduction of oxidative stress and improvement of autophagic flux. These findings indicate that NMN may hold great potential as a therapeutic approach for myocardial abnormalities under microgravity conditions.

IntroductionAprocitentan, is an orally active, once-daily administered, dual endothelin receptor antagonist that was recently approved for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs.MethodsThe potential of aprocitentan to affect the QT interval was investigated in this thorough QT/QTc study that was performed as a multiple-dose, randomized, double-blind, placebo- and moxifloxacin-controlled (open-label), crossover study in healthy male and female subjects. Concentration-QT modeling, using a linear mixed-effects model, was performed on data extracted from continuous Holter electrocardiogram recordings.ResultsOf the 48 subjects enrolled in the study, 32 subjects completed study treatment. The main reasons for stopping study treatment were the occurrence of adverse events and withdrawal of consent. The dosing regimen of 25 mg aprocitentan o.d. (the highest approved therapeutic dose in the European Union; C_max = 3.68 µg/mL) was safe and well tolerated; the supratherapeutic dosing regimen of 100 mg aprocitentan o.d. showed limited tolerability. Results indicated that ΔΔQTcF increased with increasing aprocitentan concentrations. The predicted upper bound of the 2-sided 90% ΔΔQTcF confidence interval exceeded the 10 ms threshold of regulatory concern at 16.10 µg/mL, which was close to the geometric mean maximum concentration (ie, 16.77 µg/mL) obtained with a 100 mg supratherapeutic dose.ConclusionsAt the highest therapeutic dose of 25 mg, there was no clinically significant prolongation of QTc. The risk of QT prolongation with therapeutic doses of aprocitentan is considered low.

BackgroundWhile PCSK9 inhibition has proven safe and effective, there is limited research on using intravascular ultrasound (IVUS) to assess the impact of atorvastatin combined with PCSK9 inhibitors on borderline coronary lesions.MethodsFrom June 2022 to June 2025, a detailed analysis of biochemical markers, coronary angiography (CAG), and IVUS was conducted on 69 patients with borderline coronary lesions after different treatments.ResultsOf the 69 patients enrolled, 60 completed the 48-week study. All groups showed significant low-density lipoprotein cholesterol (LDL-C) reductions, with Group C (Alirocumab + Atorvastatin) having the largest decrease from 3.64 to 1.48 (P < .001). At 48 weeks, arterial lumen volumes increased in all groups, but Group C's was significantly larger than Groups A (Alirocumab + placebo) and B (Atorvastatin + placebo) (P = .038). Group C also had a greater reduction in plaque volume compared to Groups A and B (P = .041).ConclusionAlirocumab and Atorvastatin together significantly lowered LDL-C levels and improved the vascular environment, notably reversing plaque in patients with borderline coronary lesions.

Background: Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model.

Methods: Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured.

Results: At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both p < 0.001), with no difference in sBP between vehicle and SZC (p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (p < 0.01); urine sodium increased with SZC (p < 0.01); and urine calcium increased with patiromer (p < 0.01). Urine phosphorus decreased with patiromer (p < 0.01) but increased with SZC (p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017).

Conclusions: After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP.

Objective: This study evaluates the 3-year clinical outcomes of high Killip grade (III/IV) acute myocardial infarction (AMI) patients treated with either β-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEI) or BB and angiotensin receptor blockers (ARB).

Methods: A total of 13,105 patients were registered at the Korea Acute Myocardial Infarction Registry at the National Institute of Health (KAMIR-NIH). Among them, 871 patients with high Killip classification AMI were divided into the BB + ACEI group (n = 489) and the BB + ARB group (n = 381). Following propensity score matching, 343 patients were selected in each group. All patients completed a 3-year follow-up period.

Results: The results indicate no significant differences between the BB + ACEI group and BB + ARB group in terms of cardiac death, recurrent myocardial infarction, and the rate of repeat percutaneous coronary intervention. However, the BB + ACEI group exhibited significantly lower risks in major adverse cardiac events (HR = 0.574, 95% CI: 0.421-0.783, p < .001), all-cause mortality (HR = 0.561, 95% CI: 0.404-0.778, p = .001), and non-cardiac death (HR = 0.365, 95% CI: 0.208-0.639, p < .001) compared to the BB + ARB group.

Conclusion: Our results suggest that BB + ACEI treatment is more beneficial than BB + ARB for high Killip grade AMI patients. Additionally, the BB + ACEI group has a superior preventative effect on mortality compared to the BB + ARB group.