Leu27 IGF-II-induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling.

The insulin-like growth factor II receptor (IGF-IIR) induces myocardial hypertrophy under various pathological conditions like diabetes and hypertension via G protein receptors like Gαq or Gαs. Increased expression of the ligand IGF II and IGF-IIR induces pathological hypertrophy through downstream signaling mediators such as calcineurin, nuclear factor of activated T cells 3 and calcium-calmodulin (CaM)-dependent kinase II (CaMKII)-histone deacetylase 4 (HDAC4). The dried stigma of Crocus sativus L. (saffron) has a long repute as a traditional medicine against various disorders. In the present study, we have investigated whether C. sativus extract (CSE) canameliorate Leu27 IGF-II triggered hypertrophy and have elucidated the underlying mechanism of protection. Additionally, the effects of oleic acid (OA), an activator of calcineurin and CaMKII was investigated thereof. The results demonstrate that CSE can ameliorate Leu27 IGF-II-induced hypertrophy seemingly through regulation of calcineurin-NFAT3 and CaMKII-HDAC4 signaling cascade.

Association Between Gestational Diabetes Mellitus and Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies With a Quantitative Bias Analysis of Uncontrolled Confounding.

BACKGROUND: Whether individuals with gestational diabetes mellitus (GDM) had an increased risk of hypertension remains unclear. We conducted a systematic literature review and meta-analysis to examine the association between GDM and hypertension and performed a quantitative bias analysis to quantify the impact of uncontrolled confounding due to antenatal psychological stress. METHODS: We searched databases (PUBMED, EMBASE, and Web of Science) through 2022/11. Eligible studies were cohort studies that reported the association of GDM with hypertension. We assessed the risk of bias using the Newcastle-Ottawa Scale for cohort studies. We pooled adjusted risk ratios with 95% CIs using a random effects model. We performed the quantitative bias analysis using the bias formula. RESULTS: We included 15 cohort studies, with a total of 3 959 520 (GDM, 175 378; non-GDM, 3 784 142) individuals. During the follow-up of 2 to 20 years, 106 560 cases of hypertension were reported. We found that GDM was associated with a higher risk of hypertension (pooled risk ratio, 1.78 [95% CI, 1.47, 2.17]). The risk ratio was lower among cohorts assessing incident (1.58 [95% CI, 1.29, 1.95]) than prevalent hypertension (2.60 [95% CI, 2.40, 2.83]). However, other subgroup analyses showed no differences. The quantitative bias analysis revealed that if the uncontrolled confounder of antenatal psychological stress was additionally adjusted, the positive association between GDM and hypertension would attenuate slightly (≤18%) but remains positive. CONCLUSIONS: Limitations of this study included residual confounding and discrepancies in GDM and hypertension ascertainments. Our findings indicate that GDM is positively associated with hypertension after the index pregnancy.