ArticleThe Journal of thoracic and cardiovascular surgery2016
Calpain inhibition improves collateral-dependent perfusion in a hypercholesterolemic swine model of chronic myocardial ischemia.
Article in The Journal of thoracic and cardiovascular surgery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 22 citations in OpenAlex.
- Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.Free radical biology & medicine · 2023Article
- One Billion hiPSC-Cardiomyocytes: Upscaling Engineered Cardiac Tissues to Create High Cell Density Therapies for Clinical Translation in Heart Regeneration.Bioengineering (Basel, Switzerland) · 2023Article
- Efficacy of leupeptin in treating ischemia in a rat hind limb model.Physiological reports · 2022Article
- Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.The Journal of thoracic and cardiovascular surgery · 2022Article
- Preclinical models of congestive heart failure, advantages, and limitations for application in clinical practice.Frontiers in physiology · 2022Review
- Coronary microvascular adaptations distal to epicardial artery stenosis.American journal of physiology. Heart and circulatory physiology · 2021Review
- Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome.Journal of the American Heart Association · 2019Article
- Enhanced coronary arteriolar contraction to vasopressin in patients with diabetes after cardiac surgery.The Journal of thoracic and cardiovascular surgery · 2018Article
- Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia.Journal of the American Heart Association · 2018Article
- Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction.Advances in pharmacology (San Diego, Calif.) · 2018Review
- Novel molecular targets for coronary angiogenesis and ischemic heart disease.Coronary artery disease · 2017Review
- Diabetes and Cardioplegia.Journal of nature and science · 2017Article
- Calpain inhibition decreases inflammatory protein expression in vessel walls in a model of chronic myocardial ischemia.Surgery · 2017Article
- Calpain inhibition modulates glycogen synthase kinase 3β pathways in ischemic myocardium: A proteomic and mechanistic analysis.The Journal of thoracic and cardiovascular surgery · 2017Article
- Glycogen Synthase Kinase 3β Inhibition Improves Myocardial Angiogenesis and Perfusion in a Swine Model of Metabolic Syndrome.Journal of the American Heart Association · 2016Article
- Role of Calpain in Pathogenesis of Human Disease Processes.Journal of nature and science · 2016Article
- Calpains and Coronary Vascular Disease.Circulation journal : official journal of the Japanese Circulation Society · 2016Review
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9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCalpain overexpression is implicated in aberrant angiogenesis. We hypothesized that calpain inhibition (MDL28170) would improve collateral perfusion in a swine model with hypercholesterolemia and chronic myocardial ischemia.
methodsYorkshire swine fed a high cholesterol diet for 4 weeks underwent surgical placement of an ameroid constrictor to their left circumflex coronary artery. Three weeks later, animals received no drug, high cholesterol control group (n = 8); low-dose calpain inhibition (0.12 mg/kg; n = 9); or high-dose calpain inhibition (0.25 mg/kg; n = 8). The heart was harvested after 5 weeks.
resultsMyocardial perfusion in ischemic myocardium significantly improved with high-dose calpain inhibition at rest and with demand pacing (P = .016 and .011). Endothelium-dependent microvessel relaxation was significantly improved with low-dose calpain inhibition (P = .001). There was a significant increase in capillary density, with low-dose calpain inhibition and high-dose calpain inhibition (P = .01 and .01), and arteriolar density with low-dose calpain inhibition (P = .001). Calpain inhibition significantly increased several proangiogenic proteins, including vascular endothelial growth factor (P = .02), vascular endothelial growth factor receptor 1 (P = .003), vascular endothelial growth factor receptor 2 (P = .003), and talin, a microvascular structural protein (P = .0002). There was a slight increase in proteins implicated in endothelial-dependent (nitric oxide mediated) relaxation, including extracellular signal-regulated kinase, phosphorylated extracellular signal-regulated kinase, and inducible nitric oxide synthase with calpain inhibition.
conclusionsIn the setting of hypercholesterolemia, calpain inhibition improved perfusion, with a trend toward increased collateralization on angiography and increased capillary and arteriolar densities in ischemic myocardium. Calpain inhibition also improved endothelium-dependent microvessel relaxation and increased expression of proteins implicated in angiogenesis and vasodilatation.
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