Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening
| Autor: | Marc van Bilsen, Oana Sorop, Isabel T.N. Nguyen, Marianne C. Verhaar, Ilkka Heinonen, Kelly Stam, Robert-Jan van Geuns, Caroline Cheng, Daphne Merkus, Vincent J. de Beer, Anton H. van den Meiracker, Yanti Octavia, Matthijs Van Kranenburg, Robin Verjans, Piotr A. Wielopolski, Gabriel P. Krestin, Wolfgang A. Linke, Jolanda van der Velden, Dirk J. Duncker, Jaap A. Joles, Walter Paulus, Jens van de Wouw, A.H. Jan Danser, Richard W. B. van Duin |
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| Přispěvatelé: | Cardiology, Radiology & Nuclear Medicine, Internal Medicine, Physiology, ACS - Heart failure & arrhythmias, Amsterdam Reproduction & Development (AR&D), Cardiologie, RS: CARIM - R2.02 - Cardiomyopathy, Fysiologie |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Sus scrofa Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Comorbidity Coronary Artery Disease 030204 cardiovascular system & hematology Systemic inflammation Ventricular Function Left Ventricular Dysfunction Left 0302 clinical medicine Diastole Risk Factors Medicine POPULATION METABOLIC SYNDROME education.field_of_study Ejection fraction NONCARDIAC COMORBIDITIES STIFFNESS Coronary Vessels 3. Good health Coronary circulation Cardiac Disease and Heart Failure Hypertension Renovascular medicine.anatomical_structure PRESERVED EJECTION FRACTION Cardiology HEART-FAILURE Female Endothelium/nitric oxide medicine.symptom Cardiology and Cardiovascular Medicine medicine.medical_specialty Hypercholesterolemia Population Heart failure Diabetes Mellitus Experimental MECHANISMS 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center INFLAMMATION Physiology (medical) Internal medicine PRESSURE-OVERLOAD Humans Animals Translational studies education Pressure overload business.industry Microcirculation Myocardium Editorials Stroke Volume Original Articles ta3121 medicine.disease Fibrosis MODEL Oxidative Stress 030104 developmental biology Myocardial fibrosis Oxidant stress business |
| Zdroj: | Cardiovascular Research, 114, 7, pp. 954-964 Cardiovascular Research, 114(7), 954-964. Oxford University Press Cardiovascular Research, 114, 954-964 Sorop, O, Heinonen, I, Van Kranenburg, M, Van De Wouw, J, De Beer, V J, Nguyen, I T N, Octavia, Y, Van Duin, R W B, Stam, K, Van Geuns, R J, Wielopolski, P A, Krestin, G P, Van Den Meiracker, A H, Verjans, R, Van Bilsen, M, Danser, A H J, Paulus, W J, Cheng, C, Linke, W A, Joles, J A, Verhaar, M C, Van Der Velden, J, Merkus, D & Duncker, D J 2018, ' Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening ', Cardiovascular Research, vol. 114, no. 7, pp. 954-964 . https://doi.org/10.1093/cvr/cvy038 Cardiovascular Research |
| ISSN: | 0008-6363 |
| Popis: | Aims More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure–volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction. |
| Databáze: | OpenAIRE |
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