Andrographolide improves the dysfunction of endothelial progenitor cells from angiotensin II-induced hypertensive mice through SIRT1 signaling

Platelet-derived growth factor (PDGF)-induced changes in vascular smooth muscle cells (VSMCs) stimulate vascular remodeling, resulting in vascular diseases such as pulmonary arterial hypertension. VSMCs communicate with endothelial cells through extracellular vesicles (EVs) carrying cargos, including microRNAs. To understand the molecular mechanisms through which PDGF-stimulated pulmonary artery smooth muscle cells (PASMCs) interact with pulmonary artery endothelial cells (PAECs) under pathological conditions, we investigated the crosstalk between PASMCs and PAECs via extracellular vesicle miR-409-5p under PDGF stimulation. miR-409-5p expression was upregulated in PASMCs upon PDGF signaling, and it was released into EVs. The elevated expression of miR-409-5p was transported to PAECs and led to their impaired function, including reduced NO release, which consequentially resulted in enhanced PASMC proliferation. We propose that the positive regulatory loop of PASMC-extracellular vesicle miR-409-5p-PAEC is a potential mechanism underlying the proliferation of PASMCs under PDGF stimulation. Therefore, miR-409-5p may be a novel therapeutic target for the treatment of vascular diseases, including pulmonary arterial hypertension.

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The central mechanisms of electroacupuncture at LR3 in the treatment of spontaneous hypertension: a PET and mRNA transcriptome study

Li,

Peng,

et al. 2024

Front. Cardiovasc. Med.

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ObjectiveTo reveal the efficacy and potential mechanisms of electroacupuncture (EA) in treating hypertension.MethodsMale spontaneously hypertensive rats (SHRs) were randomly assigned to the SHR group, EA group, and Sham-EA group, with Wistar-Kyoto rats (WKY) as the normal control group. SHRs in the EA group received electroacupuncture at the bilateral Taichong (LR3) acupoints for 7 consecutive days. Evaluation of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) was conducted. Positron emission tomography-computed tomography (PET-CT) was employed to explore the active brain regions associated with acupuncture-induced blood pressure reduction. Furthermore, mRNA expression profiling was analyzed in the active brain regions to identify differentially expressed genes, and quantitative polymerase chain reaction (qPCR) was used to validate the mRNA expression of differentially expressed genes in the active brain region.ResultsEA reduced elevated SBP, DBP, MAP and HR in SHR. PET-CT revealed that EA decreased glucose metabolism in the hypothalamus. Genomic analysis suggested that, compared to the SHR group, the differentially expressed genes in the hypothalamus of the EA group included Nr4a1, Sirt1, Trh, GPR88, Cck, and Th. EA downregulated the mRNA expression of Th, Trh, Gpr88, and Nr4a1, while upregulating the expression of Sirt1 and Cck at the mRNA level.ConclusionEA may exert a unique antihypertensive effect in the hypothalamus of SHR, involving the modulation of sympathetic nerve activity, neuroinflammation, and oxidative stress response.

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Andrographolide improves the dysfunction of endothelial progenitor cells from angiotensin II-induced hypertensive mice through SIRT1 signaling

Cited by 3 publications

References 32 publications

Andrographolide induced heme oxygenase-1 expression in MSC-like cells isolated from rat bone marrow exposed to environmental stress

Andrographolide induced heme oxygenase-1 expression in MSC-like cells isolated from rat bone marrow exposed to environmental stress

Platelet-derived growth factor-stimulated pulmonary artery smooth muscle cells regulate pulmonary artery endothelial cell dysfunction through extracellular vesicle miR-409-5p

The central mechanisms of electroacupuncture at LR3 in the treatment of spontaneous hypertension: a PET and mRNA transcriptome study

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