Myocardial infarction-induced hippocampal microtubule damage by cardiac originating microRNA-1 in mice

Journal of Molecular and Cellular Cardiology
Lin-Lin SunJing Ai

Abstract

Cardiovascular diseases are risk factors for dementia, but the mechanisms remain elusive. Here, we report that myocardial infarction (MI) generated by the ligation of the left coronary artery (LCA) could lead to increased miR-1 levels in the hippocampus and blood with neuronal microtubule damage and decreased TPPP/p25 protein expression in the hippocampus. These changes could be prevented by a knockdown of miR-1 using hippocampal stereotaxic injections of anti-miR-1 oligonucleotide fragments carried by a lentivirus vector (lenti-pre-AMO-miR-1). TPPP/p25 protein was downregulated by miR-1 overexpression, upregulated by miR-1 inhibition, and unchanged by binding-site mutations or miR-masks, indicating that the TPPP/p25 gene was a potential target for miR-1. Additionally, the pharmacological inhibition of sphingomyelinase by GW4869 to inhibit exosome generation in the heart significantly attenuated the increased miR-1 levels in the hippocampi of transgenic (Tg) and MI mice. Collectively, the present study demonstrates that MI could directly lead to neuronal microtubule damage independent of MI-induced chronic brain hypoperfusion but involving the overexpression of miR-1 in the hippocampus that was transported by exosomes from infa...Continue Reading

Citations

Oct 6, 2020·Frontiers in Physiology·Raquel Figuinha Videira, Paula A da Costa Martins
Jun 25, 2020·Current Cardiology Reports·Gianlorenzo DanieleFederica Del Monte
Mar 21, 2021·Free Radical Biology & Medicine·Changhai TianIrving H Zucker
Aug 31, 2021·Oxidative Medicine and Cellular Longevity·Chengyang XuZhipeng Cao

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