Vascular smooth muscle cell-specific miRNA-214 deficiency alleviates simulated microgravity-induced vascular remodeling.

The human cardiovascular system has evolved to accommodate the gravity of Earth. Microgravity during spaceflight has been shown to induce vascular remodeling, leading to a decline in vascular function. The underlying mechanisms are not yet fully understood. Our previous study demonstrated that miR-214 plays a critical role in angiotensin II-induced vascular remodeling by reducing the levels of Smad7 and increasing the phosphorylation of Smad3. However, its role in vascular remodeling evoked by microgravity is not yet known. This study aimed to determine the contribution of miR-214 to the regulation of microgravity-induced vascular remodeling. The results of our study revealed that miR-214 expression was increased in the forebody arteries of both mice and monkeys after simulated microgravity treatment. In vitro, rotation-simulated microgravity-induced VSMC migration, hypertrophy, fibrosis, and inflammation were repressed by miR-214 knockout (KO) in VSMCs. Additionally, miR-214 KO increased the level of Smad7 and decreased the phosphorylation of Smad3, leading to a decrease in downstream gene expression. Furthermore, miR-214 cKO protected against simulated microgravity induced the decline in aorta function and the increase in stiffness. Histological analysis showed that miR-214 cKO inhibited the increases in vascular medial thickness that occurred after simulated microgravity treatment. Altogether, these results demonstrate that miR-214 has potential as a therapeutic target for the treatment of vascular remodeling caused by simulated microgravity.

Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway.

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.

Simulated spaceflight-induced cardiac remodeling is modulated by gut microbial-derived trimethylamine N-oxide.

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.