Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia

Autor: Ilkka Heinonen, Sietse Jan Koopmans, Dirk J. Duncker, Oana Sorop, Richard W. B. van Duin, Daphne Merkus, Nienke S. van Ditzhuijzen, Vincent J. de Beer, Wim J. van der Giessen, Zhichao Zhou, A.H. Jan Danser, Mieke van den Heuvel
Přispěvatelé: Cardiology, Internal Medicine
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Animal Nutrition
Small-Conductance Calcium-Activated Potassium Channels
Swine
Physiology
Vasodilator Agents
Sus scrofa
030204 cardiovascular system & hematology
Coronary artery disease
0302 clinical medicine
Coronary microvascular dysfunction
Medicine
Endothelin-1
Diabetes
digestive
oral
and skin physiology
food and beverages
Intermediate-Conductance Calcium-Activated Potassium Channels
Receptor
Endothelin A
Coronary Vessels
Receptor
Endothelin B
Diervoeding
Plaque
Atherosclerotic
Vasodilation
Feature (computer vision)
Cardiology
lipids (amino acids
peptides
and proteins)
Long term diabetes
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
medicine.medical_specialty
Hypercholesterolemia
S-Nitroso-N-Acetylpenicillamine
Bradykinin
Diet
High-Fat
Nitric Oxide
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Experimental
03 medical and health sciences
SDG 3 - Good Health and Well-being
Physiology (medical)
Internal medicine
Diabetes mellitus
Animals
Large-Conductance Calcium-Activated Potassium Channels
business.industry
nutritional and metabolic diseases
medicine.disease
Endothelin 1
030104 developmental biology
Vasoconstriction
Microvessels
business
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology, 311(6), H1339-H1351. American Physiological Society
American Journal of Physiology : Heart and Circulatory Physiology, 311(6), H1339-H1351
American Journal of Physiology : Heart and Circulatory Physiology 311 (2016) 6
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00458.2015
Popis: Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo of DM and high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation and attenuated endothelin (ET)-1-mediated vasoconstriction. Here we studied the progression of CMD after 15 mo in the same animal model of CAD. Ten male swine were fed a HFD in the absence (HFD, n = 5) or presence of streptozotocin-induced DM (DM + HFD, n = 5). Responses of small (∼300-μm-diameter) coronary arteries to BK, ET-1, and the nitric oxide (NO) donor S-nitroso- N-acetylpenicillamine were examined in vitro and compared with those of healthy (Normal) swine ( n = 12). Blood glucose was elevated in DM + HFD (17.6 ± 4.5 mmol/l) compared with HFD (5.1 ± 0.4 mmol/l) and Normal (5.8 ± 0.6 mmol/l) swine, while cholesterol was markedly elevated in DM + HFD (16.8 ± 1.7 mmol/l) and HFD (18.1 ± 2.6 mmol/l) compared with Normal (2.1 ± 0.2 mmol/l) swine (all P < 0.05). Small coronary arteries showed early atherosclerotic plaques in HFD and DM + HFD swine. Surprisingly, DM + HFD and HFD swine maintained BK responsiveness compared with Normal swine due to an increase in NO availability relative to endothelium-derived hyperpolarizing factors. However, ET-1 responsiveness was greater in HFD and DM + HFD than Normal swine (both P < 0.05), resulting mainly from ETB receptor-mediated vasoconstriction. Moreover, the calculated vascular stiffness coefficient was higher in DM + HFD and HFD than Normal swine (both P < 0.05). In conclusion, 15 mo of DM + HFD, as well as HFD alone, resulted in CMD. Although the overall vasodilation to BK was unperturbed, the relative contributions of NO and endothelium-derived hyperpolarizing factor pathways were altered. Moreover, the vasoconstrictor response to ET-1 was enhanced, involving the ETB receptors. In conjunction with our previous study, these findings highlight the time dependence of the phenotype of CMD.
Databáze: OpenAIRE
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