Human coronary microvascular contractile dysfunction associates with viable synthetic smooth muscle cells

Kim A Dora*, Lyudmyla Borysova, Xi Ye, Chloe Powell, Timea Z Beleznai, Christopher P Stanley, Vito D Bruno, Tobias Starborg, Errin Johnson, Anna Pielach, Michael Taggart, Nicola Smart, Raimondo Ascione

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

AimsCoronary microvascular smooth muscle cells (SMCs) respond to luminal pressure by developing myogenic tone (MT), a process integral to the regulation of microvascular perfusion. The cellular mechanisms underlying poor myogenic reactivity in patients with heart valve disease are unknown and form the focus of this study.Methods and ResultsIntramyocardial coronary micro-arteries (IMCAs) isolated from human and pig right atrial appendage (RA) and left ventricular (LV) biopsies were studied using pressure myography combined with confocal microscopy. All RA- and LV-IMCAs from organ donors and pigs developed circa 25% MT. In contrast, 44% of human RA-IMCAs from 88 patients with heart valve disease had poor (<10%) MT yet retained cell viability and an ability to raise cytoplasmic Ca2+ in response to vasoconstrictor agents. Comparing across human heart chambers and species we found that based on patient medical history and six tests, the strongest predictor of poor MT in IMCAs was increased expression of the synthetic marker caldesmon relative to the contractile marker SM-myosin heavy chain. In addition, high resolution imaging revealed a distinct layer of longitudinally-aligned SMCs between ECs and radial SMCs, and we show poor MT was associated with disruptions in these cellular alignments.ConclusionsThese data demonstrate the first use of atrial and ventricular biopsies from patients and pigs to reveal that impaired coronary MT reflects a switch of viable SMCs towards a synthetic phenotype, rather than a loss of SMC viability. These arteries represent a model for further studies of coronary microvascular contractile dysfunction.
Original languageEnglish
Article numbercvab218
JournalCardiovascular Research
Early online date26 Jun 2021
DOIs
Publication statusE-pub ahead of print - 26 Jun 2021

Keywords

  • human
  • coronary arterioles
  • coronary microvascular function
  • myogenic tone
  • ultrastructure
  • Ca2+ signalling
  • synthetic phenotype
  • smooth muscle cell
  • heart valve disease
  • microvascular perfusion

Fingerprint

Dive into the research topics of 'Human coronary microvascular contractile dysfunction associates with viable synthetic smooth muscle cells'. Together they form a unique fingerprint.

Cite this