Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Background: Retinal imaging provides a noninvasive window into systemic microvascular health. Many optical coherence tomography studies of cardiovascular disease have focused on mean retinal thickness, which may be influenced by demographic and ocular factors. Whether intereye retinal asymmetry provides additional prognostic information beyond mean retinal thickness remains unclear. Methods: We conducted a prospective cohort study in the UK Biobank including 46 836 participants with bilateral optical coherence tomography imaging. Across the 4 end point‐specific analyses, the maximum follow‐up was 12.86 years, and median follow‐up ranged from 9.22 to 9.38 years. Intereye absolute difference and intereye percentage difference were calculated for multiple retinal layers. Associations with incident coronary heart disease, myocardial infarction, atrial fibrillation, and heart failure were evaluated using multivariable Cox models. Dose–response analyses and predictive performance comparisons were performed. Proteomic data were integrated to explore circulating molecular signatures associated with retinal asymmetry and cardiovascular outcomes. Results: Greater retinal asymmetry was consistently observed in participants who developed cardiovascular disease. Retinal nerve fiber layer asymmetry showed the most consistent associations with incident outcomes, with hazard ratios ranging from ∼1.07 for atrial fibrillation to 1.15 for heart failure per SD increase. Models including retinal nerve fiber layer asymmetry modestly improved cardiovascular risk prediction compared with mean retinal thickness alone. Exploratory proteomic analyses suggested associations between retinal nerve fiber layer asymmetry and circulating signatures related to extracellular matrix remodeling, inflammation, and insulin‐like growth factor signaling. Conclusions: Intereye retinal asymmetry, particularly retinal nerve fiber layer asymmetry, is associated with incident cardiovascular disease and may represent a candidate optical coherence tomography‐derived marker for cardiovascular risk stratification.

The causal relationships between blood cell traits and cardiac and aortic structure and function remain unclear. In this 2-sample Mendelian randomization study, we investigated the causal genetic relationships between 15 blood cell traits and 100 cardiovascular magnetic resonance imaging traits. instrumental variables comprised independent genetic variants significantly associated with 7 red blood cell traits, 6 white blood cell traits, and 2 platelet traits. The cardiovascular magnetic resonance traits, derived from 7 distinct genome-wide association studies, served as preclinical endophenotypes characterizing aortic segment and cardiac chamber structure and function. Primary effects were estimated using the inverse-variance weighted method, with sensitivity analyses addressing horizontal pleiotropy. Multivariable and reverse Mendelian randomization analyses were also performed. Genetically predicted elevations in red blood cell count, hemoglobin concentration, and hematocrit (HCT) were associated with reduced volumes across various heart chambers and aortic diameters. Elevated hemoglobin and HCT levels correlate with diminished ventricular volumes and masses. Conversely, genetically predicted higher lymphocyte count was predominantly associated with reduced aortic diameter. Additionally, increased HCT was linked to enhanced left ventricular global longitudinal strain, whereas red cell distribution width was positively associated with aortic and thoracic aortic diameters. This study suggests potential causal relationships between blood cell traits and cardiac and aortic remodeling. These findings indicate that risk assessment and monitoring strategies incorporating blood cell traits may represent novel approaches for cardiovascular disease prevention.

Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, observational studies are susceptible to confounding factors and reverse causality. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 patient phenotypes (susceptibility, hospitalization, and severity) and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. In addition, we performed sensitivity analyses using RadialMR, MRPRESSO, MR Egger regression, Cochran’s Q statistic, and Leave-one-out analysis. Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR: 2.428, 95% confidence interval[CI]:1.493-3.947, P _IVW =3.579 ×10 ^-4 ) and RNFL thickness (OR: 1.735,95%CI:1.198-2.513, P _IVW =3.580×10 ^-3 ). The results after excluding MRPRESSO and RadialMR to identify outliers and SNPs associated with confounding factors showed RNFL thickness(OR:1.800,95%CI: 1.192-2.717, P _IVW =5.147×10 ^-3 ).Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. In conclusion, the host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID-19 susceptibility in retinopathy.

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