ABSTRACT
Atherosclerosis is a complex progressive disease involving intertwined biological mechanisms. We aimed to identify miRNA expression dynamics at the early stages of atherosclerosis using a large swine model (Wisconsin Miniature Swine, WMS). A total of 18 female pigs; 9 familial hypercholesterolemic (WMS-FH) and 9 normal control swine (WMS-N) were studied. miRNA sequencing was performed on plasma cell-free RNA at 3, 6, and 9 months of age. RT-qPCR validated DE miRNAs in a new cohort of animals (n = 30) with both sexes. Gene ontology and mRNA targets for DE miRNAs were identified. In vivo multimodality imaging and histopathology were performed to document the presence of atherosclerosis at termination. 20, 19, and 9 miRNAs were significantly DE between the groups at months 3, 6, and 9, respectively. Most DE miRNAs and their target genes are involved in human atherosclerosis development. Coronary atherosclerosis was documented in 7/9 WMS-FH pigs. Control animals had no lesions. miR-138, miR-152, miR-190a, and miR-196a showed a significant diagnostic power at month 3, whereas miR-486, miR-126-3p, miR-335, and miR-423-5p were of significant diagnostic power at month 9. In conclusion, specific DE miRNAs with significant discriminatory power may be promising biomarkers for the early detection of coronary atherosclerosis.
Subject(s)
Atherosclerosis , Circulating MicroRNA , Coronary Artery Disease , Hyperlipoproteinemia Type II , MicroRNAs , Humans , Male , Female , Swine , Animals , Coronary Artery Disease/genetics , MicroRNAs/metabolism , Atherosclerosis/genetics , Atherosclerosis/pathology , Biomarkers , Hyperlipoproteinemia Type II/genetics , Circulating MicroRNA/genetics , Swine, Miniature/genetics , Swine, Miniature/metabolismABSTRACT
BACKGROUND: The efficacy of coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) among patients with stable chest pain has been studied in several trials with conflicting results. METHODS: We performed a systematic review and meta-analysis comparing CCTA first versus direct ICA among patients with stable chest pain, who were initially referred to ICA. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials comparing the 2 strategies. Risk ratios (RRs) and mean differences with 95% CIs were computed for binary and continuous outcomes, respectively. RESULTS: Five randomized controlled trials with a total of 5727 patients were included, of whom 51.1% were referred to CCTA and 22.5% of patients had evidence of ischemia on a prior functional test. In the follow-up ranging from 1 to 3.5 years, 660 of the 2928 patients randomized to CCTA first underwent ICA (23%). Patients who underwent CCTA had lower rates of coronary revascularization (RR, 0.74 [95% CI, 0.66-0.84]; P<0.001) and stroke (RR, 0.50 [95% CI, 0.26-0.98]; P=0.043). Cardiovascular mortality (RR, 0.55 [95% CI, 0.24-1.23]; P=0.146), major adverse cardiovascular events (RR, 0.84 [95% CI, 0.64-1.10]; P=0.198), nonfatal myocardial infarction (RR, 1.09 [95% CI, 0.63-1.88]; P=0.768), and cardiovascular hospitalizations (RR, 0.91 [95% CI, 0.59-1.39]; P=0.669) did not differ significantly between groups. CONCLUSIONS: In patients with stable chest pain referred for ICA, CCTA avoided the need for ICA in 77% of patients otherwise referred for ICA. CCTA was associated with a reduction in the rates of coronary revascularization and stroke compared with direct ICA. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023383143.
