Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts’ health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague–Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K⁺ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

Hypoxia leads to endothelial dysfunction and increased blood–brain barrier (BBB) permeability, promoting the incidence of diseases such as stroke and acute high-altitude illness. Brain microvascular endothelial cells (BMECs) are important structural and functional components of the BBB; however, the molecular changes that occur in BMECs during hypoxia remain unknown. We reported the molecular and functional changes in BMECs under hypoxia through whole-transcriptome sequencing, small RNA microarray, TMT quantitative proteomic, and untargeted metabolomic analyses. We found that hypoxia affected pathways such as ncRNA processing, the HIF-1 signaling pathway, the cell cycle, DNA replication, glucose metabolism, protein synthesis, and inflammation pathways. ncRNA processing was significantly downregulated. However, the levels of some miRNAs, tRNAs, tsRNAs, snoRNAs, lncRNAs, and circRNAs were significantly upregulated under hypoxia. These results suggest that ncRNAs may play an important role in oxidative stress and cellular adaptation to hypoxia, helping us understand the pathological process of BBB injury and providing potential targets for the treatment of BBB-related cerebrovascular diseases.