Angiogenesis has a great impact on human health, owing to its participation in development, wound healing and the pathogenesis of several diseases. It has been reported that let‐7a is a tumour suppressor, but whether it plays a role in angiogenesis is unclear. Here we showed that let‐7a, a microRNA conserved in vertebrates, regulated angiogenesis by concomitantly down‐regulating TGFBR3. Overexpression of let‐7a or knockdown of TGFBR3 in cell culture inhibited the tube formation and reduced migration rate. Moreover, xenograft experiments showed that overexpression of let‐7a or knockdown of TGFBR3 had smaller tumour size. Downstream genes, such as VEGFC and MMP9, were also down‐regulated in let‐7a overexpression or TGFBR3 knockdown groups. Therefore, our results revealed a novel mechanism that let‐7a regulate angiogenesis through post‐transcriptional regulation of TGFBR3.
Background: Circadian rhythms have a considerable impact on the daily physiology of the heart, and their disruption causes pathology. Several studies have revealed that circadian disruption impaired cardiac remodeling after myocardial infarction (MI); however, the underlying brain-heart mechanisms remain unknown. We aim to discuss whether circadian disruption facilitates cardiac remodeling after MI by activating sympathetic nervous system.Methods: Rats were randomly divided into three groups: Sham group (Sham), MI group (MI), and MI+ circadian disruption group (MI+Dis); rats were treated with pseudorabies virus (PRV) injections for trans-synaptic retrograde tracing; rats were randomly divided into two groups: MI+ circadian disruption + Empty Vector+ clozapine N-oxide (CNO) (Empty Vector), and MI+ circadian disruption + hM4D(Gi)+ CNO [hM4D(Gi)].Results: Circadian disruption significantly facilitated cardiac remodeling after MI with lower systolic function, larger left ventricular volume, and aggravated cardiac fibrosis. Cardiac sympathetic remodeling makers and serum norepinephrine levels were also significantly increased by circadian disruption. PRV virus-labeled neurons were identified in the superior cervical ganglion (SCG), paraventricular nucleus (PVN), and suprachiasmatic nucleus (SCN) regions. Ganglionic blockade via designer receptors exclusively activated by designer drugs (DREADD) technique suppressed the activity of sympathetic nervous system and significantly alleviated the disruption-related cardiac dysfunction.Conclusion: Circadian disruption adversely affected cardiac remodeling after MI possibly by activating sympathetic nervous system, and suppressing sympathetic activity can attenuate this disruption-related cardiac dysfunction.
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