The protective effects of Irbesartan in cognitive impairment in hypertension.

Vascular cognitive impairment (VCI) is claimed as the second most common type of dementia after Alzheimer's disease (AD), in which hypertension is a critical inducer. Currently, hypertension-induced cognitive impairment lacks clinical treatments. Irbesartan is a long-acting angiotensin receptor antagonist with promising antihypertensive properties. Our research will focus on the potential function of Irbesartan on hypertension-induced cognitive impairment. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were orally dosed with normal saline or 20 mg/kg/day Irbesartan for 14 consecutive days, with 4 groups divided shown as below: WKY, Irbesartan, SHR, SHR+ Irbesartan. Firstly, the markedly increased systolic blood pressure observed in SHR rats was signally repressed by Irbesartan on Day 7 and 14 post-dosing. Moreover, notably decreased time of exploring the novel object in the object recognition task (ORT) test, elevated escape latency, and reduced time in the target quadrant in the Morris water maze (MWM) test were observed in SHR rats, which were prominently reversed by Irbesartan. Furthermore, the declined superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) level, increased cyclin-dependent kinase-5 (CDK5) activity, and enhanced protein level of p35/p25, p-Tau (pSer214)/Tau46, and brain-derived neurotrophic factor (BDNF) were memorably rescued by Irbesartan. Lastly, the activity of cAMP/cAMP response element binding protein (CREB) signaling in the hippocampus of SHR rats was markedly repressed, accompanied by an upregulation of phosphodiesterase 4B (PDE4B), which was observably rescued by Irbesartan. Collectively, Irbesartan protected against the hypertension-induced cognitive impairment in SHR rats by regulating the cAMP/CREB signaling.

CircSCAP Aggravates Oxidized Low-density Lipoprotein-induced Macrophage Injury by Upregulating PDE3B by miR-221-5p in Atherosclerosis.

ABSTRACT: Atherosclerosis (AS) is a major risk factor for cardiovascular disease, in which circular RNAs play important regulatory roles. This research aimed to explore the biological role of circular RNA Sterol Regulatory Element Binding Transcription Factor Chaperone (circSCAP) (hsa_circ_0001292) in AS development. Real-time PCR or Western blot assay was conducted to analyze RNA or protein expression. Cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The levels of lipid accumulation-associated indicators and oxidative stress factors were detected using commercial kits. The levels of inflammatory cytokines were examined using enzyme-linked immunosorbent assay. Intermolecular interaction was verified by dual-luciferase reporter analysis or RNA pull-down analysis. CircSCAP and phosphodiesterase 3B (PDE3B) levels were elevated, whereas the miR-221-5p level was decreased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced THP-1 cells. CircSCAP absence suppressed lipid deposition, inflammation, and oxidative stress in ox-LDL-induced THP-1 cells. MiR-221-5p was a target of circSCAP, and anti-miR-221-5p largely reversed si-circSCAP-induced effects in ox-LDL-induced THP-1 cells. PDE3B was a target of miR-221-5p, and PDE3B overexpression largely counteracted miR-221-5p accumulation-mediated effects in ox-LDL-induced THP-1 cells. NF-κB signaling pathway was regulated by circSCAP/miR-221-5p/PDE3B axis in ox-LDL-induced THP-1 cells. In conclusion, circSCAP facilitated lipid accumulation, inflammation, and oxidative stress in ox-LDL-induced THP-1 macrophages by regulating miR-221-5p/PDE3B axis.

Plasma levels of miR-143 and miR-145 are associated with coronary in-stent restenosis within 1 year of follow-up after drug-eluting stent implantation.

BACKGROUND: ISR remains the major adverse outcome after percutaneous coronary intervention (PCI). MicroRNAs have been demonstrated to be associated with coronary plaque and stable in the blood and can be used as biomarkers/predictors. This study aimed to investigate whether circulating microRNAs could predict in-stent restenosis (ISR). METHODS: MicroRNA array was used to detect differently expressed microRNAs between 30 ISR patients and 30 non-ISR patients in the derivation cohort. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the microRNA array results and to detect levels of target microRNAs in the validation cohort. All patients were followed up for at least 1 year, and major adverse cardiac events (MACEs) were recorded. Univariate and multivariate logistic regression analysis were applied to find factors associated with ISR. Receiver operating characteristics (ROC) and Kaplan-Meier survival curves were used to analyze the predictive ability of the microRNA score for ISR. RESULTS: MicroRNA array and qRT-PCR showed that miR-143, 145, 425, 208, and let-7g were differently expressed between ISR patients and non-ISR patients. Multivariate analysis demonstrated that lower levels of mir-143 (OR =2.36, 95% CI: 1.43-3.67) and mir-145 (OR =2.12, 95% CI: 1.56-3.48) were associated with ISR. MicroRNA scores differed statistically between ISR patients and non-ISR patients (49.18±2.05 vs. 52.10±2.41, P<0.01) and has predictive ability for ISR with an area under the curve (AUC) of 0.8206 (95% CI: 0.7155-0.9256, P<0.01). In the validation cohort, Kaplan-Meier survival curves demonstrated that patients with higher microRNA scores have better prognosis in 1 year of follow-up. CONCLUSIONS: A lower plasma level of mir-143/145 predicts a higher risk of ISR and a worse outcome.