Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes.

BACKGROUND: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear. METHOD AND RESULTS: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes. CONCLUSION: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

The effect of type 2 diabetes mellitus on multiple obstructive coronary artery disease.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) individuals easily develop three-vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two-dimensional speckle tracking echocardiography (2-D STE) in T2DM patients with 3VD. METHODS: One hundred and three consecutive patients with confirmed 3VD CAD were enrolled and divided into two groups, while 53 patients with DM and 50 patients without. The control group was composed of 30 age- and sex-matched healthy individuals. All patients underwent 2-D STE and standard echocardiograms. The durations of DM and the level of HbA1c were also recorded. RESULT: Between the 3VD-DM and 3VD-non-DM groups, normal echocardiography did not reveal any appreciable differences. However, patients with 3VD-DM had significantly lower global longitudinal strain (GLS) than those with 3VD-non-DM (15.87 ± 2.51 vs.17.56 ± 2.72, p < .05) by 2-D STE strain measurement. Besides, patients whose duration of DM excess 5 years showed significant lower GLS than those with less than 5 years duration (14.25 ± 2.31 vs. 16.65 ± 1.96, p = .007). However, there was no difference in GLS between the 3VD-DM patients with HbA1c ≥ 7% and HbA1c < 7%. CONCLUSIONS: Compared to patients with 3VD alone, those with 3VD-DM have a lower cardiac function. In 3VD-DM patients, the duration of DM is a significant factor that contributes to cardiac function deterioration, whereas, the glucose control state has limited influence.