A recent study by Pankajakshan et al., published in Experimental and Molecular Pathology, reports the presence of neuropeptide Y (NPY)-Y2 receptors’ expression, and a pronounced cytokine-induced up-regulation of NPY-Y2 expression in carotid atherosclerotic plaques.
The study suggests that NPY, a sympathetic nervous system (SNS) neurotransmitter and stress mediator may modulate the effects of pro-inflammatory cytokines in atherosclerotic plaques of patients with carotid stenosis, and hence may affect plaque instability.
Thus, the interactions between NPY and the inflammatory cytokines released in an atherosclerotic milieu may play an important role in the regulation of atherosclerotic plaque vulnerability – its destabilization or rupture.
Neuropeptide Y (NPY) is involved in stress, mostly peripherally as a sympathetic nerve- and in some species, platelet-derived mediator and vasoconstrictor.
Neuropeptide Y is a sexually differentiated mediator of stress and may be responsible for greater cardiovascular responses in males, who express and release more NPY during stressful conditions. Elevated circulating NPY levels are observed in patients with acute myocardial infarction, angina pectoris, heart failure and hypertension where SNS activity is increased.
Sympathetic/neuropeptide Y-positive nerve fibers predominantly supply the vasculature, mostly as perivascular plexuses. Neuropeptide Y is co-released with norepinephrine (NE) upon SNS activation – particularly in conditions of high sympathetic activity large dense-cored vesicles release both NPY and NE. The ratio, however of the two neurotransmitters differs in various conditions. Tonic sympathetic activation and acute stress preferentially releases NE, whereas NPY is mostly released during prolonged and intense, or chronic stress, particularly when combined with hypoxia, and as well as in panic attacks or cold exposure.
Neuropeptide Y is a vascular mitogen, via Y1/Y5 receptors, and is angiogenic via Y2/Y5 receptors. Arterial injury activates platelet NPY and vascular Y1 receptors, inducing medial hypertrophy and neointima formation. Exogenous NPY and chronic stress augment these effects and occlude vessels with atherosclerotic-like lesions, containing thrombus and lipid-laden macrophages.
Conversely, tissue ischemia activates neuronal and platelet-derived NPY, Y2/Y5 receptors, which stimulate angiogenesis/arteriogenesis (for review, see LE Kuo and Z Zukowska, Peptides, 2007, 28: 435).
In the Experimental and Molecular Pathology study, Divya Pankajakshan and colleagues from the Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, provide evidence that smooth muscle cells in symptomatic and asymptomatic carotid plaques express NPY receptors and show differential expression of NPY receptors upon inflammatory cytokine stimulation which may consequently influence cellularity and rupture of the plaque.
The authors observed a high basal expression of NPY-Y2 receptors in the plaque sections. The symptomatic plaques showed higher expression levels of NPY-Y2 in comparison to asymptomatic plaques. Moreover, atheroma associated cytokines TNF-alpha, IFN-gamma and IL-12 decreased the density of NPY-Y1 and NPY-Y5 receptors, but increased the density of NPY-Y2 receptors in the vascular smooth muscle cells (VSMCs) of symptomatic carotid plaques.
According to the authors, an increased expression of NPY-Y2 receptors in symptomatic plaque VSMCs indicates a potential role of NPY-Y2 in plaque instability. The authors also discuss that in the presence of cytokines and NPY there is a high chance for increased in vivo angiogenesis in asymptomatic carotid plaques.
Source: Exp Mol Pathol, 2011, 90:280. doi: 10.1016/j.yexmp.2011.02.005. Epub 2011 Feb 23 Read more