Jill K Badin1, Rebecca S Bruning2, Michael Sturek3. 1. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States. 2. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States; RTI International, Global Health Technologies, Research Triangle Park, NC 27709, United States. 3. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States. Electronic address: msturek@iu.edu.
Abstract
BACKGROUND: Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS: Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ 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 Ca2+ handling dysfunction in CAD.
BACKGROUND:Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS:Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ 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 Ca2+handling dysfunction in CAD.
Authors: Sofie De Moudt; Jhana O Hendrickx; Cédric Neutel; Dorien De Munck; Arthur Leloup; Guido R Y De Meyer; Wim Martinet; Paul Fransen Journal: Front Physiol Date: 2022-06-16 Impact factor: 4.755
Authors: Ayla Hoogendoorn; Sandra den Hoedt; Eline M J Hartman; Ilona Krabbendam-Peters; Maaike Te Lintel Hekkert; Leonie van der Zee; Kim van Gaalen; Karen Th Witberg; Kristien Dorst; Jurgen M R Ligthart; Ludovic Drouet; Kim Van der Heiden; Jeanine Roeters van Lennep; Antonius F W van der Steen; Dirk J Duncker; Monique T Mulder; Jolanda J Wentzel Journal: Arterioscler Thromb Vasc Biol Date: 2019-09-26 Impact factor: 8.311
Authors: Sofie De Moudt; Jhana O Hendrickx; Cédric Neutel; Dorien De Munck; Arthur Leloup; Guido R Y De Meyer; Wim Martinet; Paul Fransen Journal: Commun Biol Date: 2022-06-17