Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention

Yang, M, Chadwick, A ORCID: 0000-0002-7399-8655, Dart, C ORCID: 0000-0002-3509-8349, Kamishima, T and Quayle, J ORCID: 0000-0003-2762-5011 (2017) Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention. PLoS One, 12 (5). e0177951-.

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Abstract

Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.

Item Type:	Article
Uncontrolled Keywords:	glycosis, bioenergetics, mitochondria, cell metabolism, smooth muscle cells, glucose metabolism, coronary arteries, glucose signalling
Depositing User:	Symplectic Admin
Date Deposited:	29 Apr 2019 10:34
Last Modified:	19 Jan 2023 00:54
DOI:	10.1371/journal.pone.0177951
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3036476

Available Versions of this Item

• Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention. (deposited 26 May 2017 13:39)
  • Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention. (deposited 29 Apr 2019 10:34) [Currently Displayed]