Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction

Neil Herring*, Nidi Tapoulal, Manish Kalla, Xi Ye, Lyudmyla Borysova, Regent Lee, Erica Dall'Armellina, Christopher Stanley, Raimondo Ascione, Chieh Ju Lu, Adrian P. Banning, Robin P. Choudhury, Stefan Neubauer, Kim Dora, Rajesh K. Kharbanda, Keith M. Channon

*Corresponding author for this work

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

15 Citations (Scopus)
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Abstract

Aims:
The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature.
Methods and Results:
Peripheral venous NPY levels were significantly higher in patients with STEMI (n=45) compared to acute coronary syndromes/stable angina (ACS/SA, n=48) or with normal coronary arteries (NC, n=16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r=0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial edema and microvascular obstruction on cardiac MRI, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100-250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1 receptor antagonist BIBO3304 (1 microM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors.
Conclusions:
High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1 receptor, and antagonists may be a useful PPCI adjunct therapy.
Original languageEnglish
Article numberehz115
Pages (from-to)1920-1929
Number of pages10
JournalEuropean Heart Journal
Volume40
Issue number24
Early online date11 Mar 2019
DOIs
Publication statusPublished - 21 Jun 2019

Keywords

  • Neuropeptide-Y
  • myocardial infarction
  • percutaneous coronary intervention
  • cardiac magnetic resonance imaging
  • microvascular function

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