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Human Coronary Micro‐artery Dysfunction is Associated with Structural and Smooth Muscle Cell Phenotypic Alterations
Author(s) -
Borysova Lyudmyla,
Ye Xi,
Smart Nicola,
Ascione Raimondo,
Dora Kim A
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.685.13
Subject(s) - vasa vasorum , coronary arteries , contraction (grammar) , electrical impedance myography , endothelium , medicine , phenotype , pathology , contractility , endothelial dysfunction , artery , cardiology , biology , anatomy , vasodilation , biochemistry , gene
Autoregulation is compromised in patients with coronary heart disease. A lack of myogenic reactivity and endothelial dysfunction each contribute to a reduced ability to control blood flow within the coronary microcirculation. Little is known how coronary arterial smooth muscle structure and phenotype links to vascular reactivity. Right atrial appendage biopsies from consented patients undergoing valve replacement surgery, and from pigs were collected at clinical standards under general anesthesia. Human and porcine arteries from right atrial appendage samples were isolated and mounted for pressure myography. Confocal imaging established vasomotor responses, cellular viability, and immunohistochemical localization of proteins. The human study complies with the Helsinki Declaration and the animal study complies with the UK Animal (Scientific Procedures) Act, 1986. Here, we compared the structural features of human patient intra‐myocardial coronary arteries (IMCAs) with equivalently handled porcine IMCAs, representing healthy, juvenile controls. More than half the human IMCAs failed to develop ≥10% myogenic tone, even those in which constituent smooth muscle cells (SMCs) could adequately mobilize intracellular Ca 2+ required for contraction. 3D confocal revealed a novel, distinct layer of longitudinally‐arranged sub‐intimal SMCs (l‐SMCs) between the endothelium and the expected circumferentially‐arranged SMCs responsible for radial contraction (r‐SMC) in the majority of human and porcine IMCAs. Contractile function strongly correlated with SMC phenotype, with the synthetic markers L‐caldesmon and vimentin highly expressed in SMCs with poor contractile function, namely the human r‐SMCs and the porcine l‐SMCs. Thus, we propose that l‐SMCs retain an immature, synthetic phenotype in healthy vessels with functional r‐SMCs but, with loss of r‐SMC function in aged patients, l‐SMCs may play a reparative role and can adopt a contractile phenotype in an attempt to restore function and control myocardial perfusion. The role of l‐SMCs in maintaining the integrity of arterial function warrants further investigation. Support or Funding Information This work was supported by the British Heart Foundation (grant numbers FS/08/033/25111, FS/13/16/30199, IG/13/5/30431, PG/18/11/33552) and by the Oxford BHF Centre of Research Excellence (RE/13/1/30181). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .