Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB375

Poster Communications

Inverse relationship between the media-to-lumen ratio and smooth muscle contractile function in resistance arteries from patients with residual cardiovascular disease

M. Bloksgaard1, S. Möller2, T. Leurgans1, A. Irmukhamedov3, L. P. Riber3, Y. Wang4, J. G. De Mey1,3

1. Institute of Molecular Medicine - Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense C, Denmark. 2. Odense Patient data Exploratory Network, Odense University Hospital, Odense C, Denmark. 3. Dept. Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, Odense C, Denmark. 4. Dept. Pharmacology and Pharmacy and Dept. of Medicine, The University of Hong Kong, State Key Laboratory of Pharmaceutical Biotechnology, Hong Kong, China.

The media-to-lumen ratio (M:L) of resistance arteries (RA) is increased in hypertension, diabetes and obesity and is an independent risk factor for the development of life threatening cardiovascular events. We hypothesized that smooth muscle contractile function (CONTR) positively relates to M:L and that both outcomes are related to and influenced unidirectionally by patient characteristics. Human pericardial RA from patients with residual cardiovascular diseases were obtained as described (1-4) after informed written consent. The Regional Committees on Health Research Ethics for Southern Denmark and the Danish Data Protection Agency approved the project. Procedures adhere to the guidelines of the World Medical Association's Declaration of Helsinki. RA (n = 503) were isolated from 128 patients and maximal contractile response and structural properties were determined by combining wire myography and histomorphometry. Relations between CONTR (maximal force/tunica media volume; mean±SD 2.60±0.94 MN/m3), M:L (median (IQR) 5.32 (4.43-6.17) %) and patient characteristics were analyzed by linear regression models using STATA after log10 transformation of the outcomes. p<0.05 was considered significant. Contrary to the hypothesis, there was a robust negative relationship between M:L and CONTR in univariate analysis (UVA), and after adjusting for patient age, gender, body mass index (BMI), mean arterial blood pressure (MAP) and diagnosis of diabetes prior to surgery (adj. p=0.029, b=-0.283 (95% CI: -0.535; -0.030)). Recent hyperglycemia (HbA1c, 38 (35-43) mmol/mol) had a small, significant increasing effect on M:L in both UVA and the model adjusted for age, gender, BMI, MAP (adj. p=0.035 b=-0.003 (0.000; 0.007)), whereas CONTR was negatively affected by HbA1c in both models (adj. p=0.041, b=-0.004 (-0.008; -0.000)). Interestingly, there was a robust, persisting negative relationship between CONTR and plasma N-terminal fragment of proBNP (BNP) in all models applied, independent of the type of surgery (coronary artery bypass grafting, valve replacement or both) both in UVA and adjusted models (age, gender, BMI, MAP, adj. p=0.964), whereas plasma BNP was not related to M:L. Finally, M:L, but not CONTR, was strongly, negatively related to RA wall stiffness (Youngs elastic modulus, 127 (91 - 159) kPa) in all models applied (p<0.0001, b=-0.627 (-0.870; -0.383)). Smooth muscle contractile function is inversely related to M:L. Quality rather than quantity of tunica media is highly important for smooth muscle function. Circulating clinically relevant diagnostic biomarkers relate differently to structure and function of the arterial smooth muscle. Further analyses will determine relations and mixed effects of other patient characteristics and patients' pharmacotherapy on the outcomes.

Where applicable, experiments conform with Society ethical requirements