Endothelial function

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The work of our group is focusing on two interacting research areas: 1. endothelial cell biology and function and 2. protection from myocardial ischemia-reperfusion injury. These areas are explored in basic studies as well as clinical investigations. We investigate the role of biologically important factors derived from endothelial cell in ischemic heart disease, atherosclerosis and vascular complications associated with diabetes. Emerging evidence indicate that the production and bioavailability of nitric oxide (NO) is regulated by arginase by competition for the substrate L-arginine. Arginase activity is upregulated in ischemic heart disease and in diabetes. Recent observations show that this is an important mechanism behind reduced bioavailability of NO in experimental animals as well as in patients with coronary artery disease and diabetes. Thus, inhibition of arginase markedly improves endothelial function and protects from myocardial ischemia-reperfusion injury. Another endothelium-derived mediator is endothelin-1 (ET-1) which also is upregulated in cardiovascular disease and diabetes. ET-1 contributes to endothelial dysfunction by increased oxidative stress and reduced bioavailability of NO. ET receptor blockade improves endothelium-dependent vasodilatation in atherosclerosis and improves insulin sensitivity in patients with insulin resistance. The role of arginase and ET-1 in cardiovascular disease is further explored in mechanistic and clinical studies.

Apart from investigating the efficacy of pharmacological interventions targeting NO bioavailability by arginase and ET-1 in ischemia-reperfusion injury we also investigate the mechanisms behind and the therapeutic effects of ischemic conditioning of the myocardium during ischemia-reperfusion. We have investigated the efficacy of local postconditioning on the development of infarct size both in experimental models and in a clinical study on patients with ST elevation myocardial infarction. Current projects are focusing on remote per- and postconditioning as an adjunct to reperfusion therapy in acute myocardial infarction.

Group description

Key publications

Combined endothelin receptor blockade evokes enhanced vasodilatation in patients with atherosclerosis.
Böhm F, Ahlborg G, Johansson B, Hansson L, Pernow J
Arterioscler. Thromb. Vasc. Biol. 2002 Apr;22(4):674-9

Dual endothelin receptor blockade acutely improves insulin sensitivity in obese patients with insulin resistance and coronary artery disease.
Ahlborg G, Shemyakin A, Böhm F, Gonon A, Pernow J
Diabetes Care 2007 Mar;30(3):591-6

Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease.
Settergren M, Böhm F, Rydén L, Pernow J
Eur. Heart J. 2008 Jul;29(14):1753-60

Arginase inhibition mediates cardioprotection during ischaemia-reperfusion.
Jung C, Gonon A, Sjöquist P, Lundberg J, Pernow J
Cardiovasc. Res. 2010 Jan;85(1):147-54

Regulation of glucose uptake by endothelin-1 in human skeletal muscle in vivo and in vitro.
Shemyakin A, Salehzadeh F, Böhm F, Al-Khalili L, Gonon A, Wagner H, et al
J. Clin. Endocrinol. Metab. 2010 May;95(5):2359-66

Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats.
Grönros J, Jung C, Lundberg J, Cerrato R, Ostenson C, Pernow J
Am. J. Physiol. Heart Circ. Physiol. 2011 Apr;300(4):H1174-81

Endothelin-1 reduces glucose uptake in human skeletal muscle in vivo and in vitro.
Shemyakin A, Salehzadeh F, Esteves Duque-Guimaraes D, Böhm F, Rullman E, Gustafsson T, et al
Diabetes 2011 Aug;60(8):2061-7

The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial.
Rafnsson A, Böhm F, Settergren M, Gonon A, Brismar K, Pernow J
Diabetologia 2012 Mar;55(3):600-7

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