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

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 ( 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 oedema and microvascular obstruction on cardiac magnetic resonance imaging, 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 Y 1 receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y 1 receptors. Conclusion 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 Y 1 receptor, and antagonists may be a useful PPCI adjunct therapy.

PRADA: Portable Reusable Accurate Diagnostics with nanostar Antennas for multiplexed biomarker screening

“…cTnI is routinely assessed in patient samples in clinical laboratories to detect myocardial damage, with a clinical range for at‐risk patients of >0.03 ng/ml 27 . NPY is a sympathetic cotransmitter and critical to cardiovascular homeostasis including cardiac remodeling and angiogenesis 28,29 . It has been correlated to stress, anxiety, and posttraumatic stress disorder 30,31 at a clinically relevant level of ≤1.5 ng/ml 32 .…”

“…27 NPY is a sympathetic cotransmitter and critical to cardiovascular homeostasis including cardiac remodeling and angiogenesis. 28,29 It has been correlated to stress, anxiety, and posttraumatic stress disorder 30,31 at a clinically relevant level of ≤1.5 ng/ml. 32 Our results showed that PRADA achieved highly sensitive detection of both biomarkers of acute myocardial infarction ideal for risk stratification.…”

Deletion of Neuropeptide Y Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction

“…NPY causes coronary microvascular constriction and reduced EF following ST-elevation MI via NPY1R that is a predominant receptor subtype in the heart (Chottova Dvorakova et al, 2008; Herring et al, 2019). So, to see whether NPY1R was involved in NPY/miR-499 and NPY/FoxO4 axis, we determined the mRNA level of miR-499 by NPY1R antagonist in MI in vitro .…”

“…NPY significantly increases infarct area in relation to the area at risk during myocardial ischemia–reperfusion (I/R) injury, which is blunted by NPY1R antagonist BIBO3304 (Herring et al, 2019). So, we want to see whether NPY1R antagonist BIBO3304 inhibits H 2 O 2 -induced cardiomyocyte apoptosis.…”

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

“…The role of cardiac afferent neurotransmission in parasympathetic function is still under investigation . Inhibition of acetylcholine release may also occur at the nerve‐myocyte interface by the high levels of norepinephrine, as well as sympathetic neuropeptides, such as neuropeptide Y, though this area remains in need of further investigation.…”