Effect of metabolic syndrome and aging on Ca2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine

Abstract

Ca dysregulation, mainly the SR Ca store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca handling dysfunction in CAD.

Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

“…To assess Ca 2+ responses, fura2 imaging was performed similar to methods previously described (44). Briefly, isolated CD4 + T cells were loaded with fura-2AM (2.5 μM, MilliporeSigma) for 45 minutes, washed, placed on poly-lysine (MilliporeSigma) coated coverslips, and placed in a superfusion chamber with physiological salt solution (PSS) containing 2 mM Ca 2+ .…”

Identification of Potential Biomarkers for CAD Using Integrated Expression and Methylation Data

“…Intriguingly, hub genes belonged to down-hyper genes and were directly correlated with the regulation of histone H3-K27 methylation according to GO enrichment analysis, which indicated an underlying association between DNA methylation and histone methylation. Regulation of calcium ion transport into the cytosol was the term enriched by down-hypo genes and has been proved to affect the progress of CAD through the coronary smooth muscle (Badin et al, 2018). Protein-protein interaction networks were established to excavate the interaction among DEMGs and filtrate the most central 10 hub genes from each group.…”

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile

“…Furthermore, IVUS-derived plaque burden is a measure that is often applied in the clinic to quantify disease burden, but is unfortunately rarely reported by other porcine model studies. Badin et al 29 and Tharp et al 30 observed average plaque burdens of 38% and 50%, respectively. We demonstrated a maximal plaque burden of 77% in the ADs, indicating the presence of lumen intruding, clinically relevant plaques.…”

“…Unlike almost all previous studies (Table XI in the online-only Data Supplement), we used adult pigs instead of juveniles for our experiments. As mentioned in the introduction, the adult age greatly improves the resemblance to human disease pathophysiology, and aging is known to enhance atherosclerosis development both in pigs 29 and in humans. 19–21 The extensive characterization of coronary atherosclerosis development in this model forms a road-map for future pathophysiological or imaging studies with this highly relevant model.…”