Biology subjects

Centner, A. M.

Publications and source records attributed to Centner, A. M..

3 recordsLinked to original sources

bioRxiv2026

Sex Effect of E-liquid Constituents on Atherosclerosis and Gut Dysbiosis in ApoE-/- Mice

RationaleThe role of sex in the effects of vaping and individual aerosolized e-liquid constituents on atherosclerosis, vascular aging, and gut microbiome remodeling remains poorly characterized. ObjectiveTo determine the contribution of e-cigarette aerosol components to vascular senescence, atherosclerosis, and gut microbiome dysbiosis in ApoE-/- mice and vascular smooth muscle cell (VSMC) viability and senescence. MethodsMale and female ApoE-/- mice were exposed to e-liquid constituents (vehicle, vehicle plus nicotine, and vehicle plus nicotine plus menthol) for 48 minutes per day, 5 days per week for 16 weeks, with vascular pathology assessed in vivo. VSMCs isolated from aortas of wild-type and ApoE-/- male and female mice were exposed to aerosolized e-liquids and evaluated for cellular senescence. ResultsExposure to all tested e-liquid formulations, including vehicle, nicotine-containing, and menthol-containing aerosols, increased atherosclerosis in both male and female mice, with the most robust effects observed in the nicotine-containing formulation and in the descending aorta. Females exhibited greater sensitivity to e-liquid exposure, with increased plaque accumulation in both the aortic arch and descending aorta, while the addition of menthol was associated with reduced plaque burden compared with nicotine alone in both sexes. Novel findings show that e-liquid exposure also altered gut microbial composition in a sex- and exposure-dependent manner, with nicotine causing the greatest dysbiosis and menthol exerting modulatory, but not restorative, effects. Notably, Alloprevotella emerged as a key discriminating genus associated with reduced plaque burden, supporting a potential link between gut microbial remodeling, inflammatory regulation, and atherosclerosis. ConclusionsThese findings demonstrate that individual e-liquid aerosol components increase atherosclerosis and alter the gut microbiome in a sex-specific manner, with nicotine producing the most pronounced pro-atherogenic effects and the addition of menthol reducing these effects, without eliminating overall atherosclerotic risk.

physiology↗

bioRxiv2024

The Role of Sex in the Effects of Smoking and Nicotine in Cardiovascular Function, Atherosclerosis, and Inflammation

cigarette smoke (CS) invokes an inflammatory response involving increased levels of circulating cytokines and chemokines, vascular dysfunction, and atherosclerosis. The role of sex and nicotine in CS effects in cardiovascular function and atherosclerosis is unexplored. To assess the role of sex, male and female C57Bl/6 WT (wild type) and ApoE-/- mice were exposed to CS and nicotine for 16 weeks to bridge this literature gap. Heart rate and endothelial function were measured in the aorta of WT mice, while plasma levels of lipids, cytokines and chemokines and aortic plaque burden was assessed in ApoE-/- mice. CS increased heart rate to similar levels in both sexes and induced a stronger impairment in endothelial function in males and more plaque in females than nicotine. Females showed a higher necrotic core area at basal compared with males, while males had a higher calcification area than females by CS. Senescence-associated GLB1/-galactosidase (SA-GLB1) activity was elevated similarly in both sexes by both treatments. Total cholesterol (TC) was elevated by CS in both sexes. CS increased triglycerides (TG), very-low density lipoprotein (VLDL) and high-density lipoprotein (HDL) only in males and low-density lipoprotein (LDL) only in females. Interleukin 17A (IL17A) was upregulated by CS and nicotine in both sexes, while CS upregulated C-X-C motif chemokine ligand 5 (CXCL5/LIX) and interleukin 1 alpha (IL1A) in males and females, respectively. Additionally, nicotine metabolism showed sex specific responses to nicotine, but not smoking. Overall, we identified sex-specific pro-atherogenic responses to CS in the lipid profile, plaque area and composition and inflammatory markers. Males present a stronger impairment in endothelia dysfunction in WT mice, while females a stronger plaque burden in ApoE-/- mice exposed to CS. Elevated HDL and estrogens in males may offer partial protection against the harmful effects of CS. In contrast, elevated LDL and a pro-inflammatory state may promote a stronger pro-atherogenic phenotype in females exposed to CS.

cell biology↗

bioRxiv2023

The Duality of Adiponectin and the Role of Sex in Atherosclerosis

Adiponectin, a hormone highly abundant in circulation, has many beneficial effects in atherosclerosis; however, gene deficiency of this hormone or its receptor have shown detrimental effects on plaque burden in mice. Our objective was to understand the role of sex and aging in the effects of adiponectin deficiency on plaque content, inflammation, and the mechanisms regulating the phenotype of adipoq-/- vascular smooth muscle cells (VSMCs). Even a 50% reduction in the expression of adiponectin led to a plaque reduction in males and an increase in females, compared with apoe-/-controls. Plaque reduction may be attributable to chemokines upregulated in males and downregulated in females. Changes in plaque were not attributed to changes in cholesterol or cardiovascular disease (CVD) markers. In old mice, both genotypes and sexes accumulated more plaque than apoe-/-. RNA sequencing of VSMCs from male mice in vitro uncovered a critical role for adiponectin in AKT signaling, regulation of the extracellular matrix, and TGF-{beta} signaling. Upregulation of AKT activity mediated proliferation and migration of adipoq-/-cells. Activation of AMPK with metformin or AdipoRon reduced AKT-dependent proliferation and migration of adipoq-/- cells but did not improve the expression of contractile genes. Anti-atherogenic mechanisms targeted the ECM in adipoq-/- cells, downregulating MMP2 and 9 and upregulating decorin. Our study uncovered sex and age-dependent effects of adiponectin deficiency in atherosclerosis.

physiology↗