Search PubMed⌕ Search

Biomedical subjects

Michael Weis

Publications and source records attributed to Michael Weis.

20 records · Page 2Linked to original sources

Vasodilator response to nifedipine in human coronary arteries with endothelial dysfunction.

The purpose of the current study was to evaluate nifedipine-induced epicardial and microvascular response in human coronary arteries with and without endothelial dysfunction and intimal thickening. The investigation was performed in 70 patients 5 +/- 5 months after heart transplantation. Coronary vasomotor function was determined with intracoronary acetylcholine adenosine, and nifedipine, respectively. Intravascular ultrasound was used to detect significant intimal hyperplasia. In a subgroup (n = 38), coronary sinus and aortic endothelin concentrations were determined. Epicardial dilation to nifedipine was significantly enhanced in coronary arteries with endothelial dysfunction (p = 0.04), whereas adenosine-induced epicardial dilation was attenuated in segments with endothelial dysfunction (p = 0.002). In cases of intimal hyperplasia, nifedipine-mediated distal vasodilation was increased compared with normal segments (p = 0.03). Coronary flow index nifedipine was enhanced in patients with microvascular endothelial dysfunction (p = 0.037). A trend was observed between high endothelin plasma levels in the coronary sinus and an increased microvasodilation to nifedipine (p = 0.04). The study shows that epicardial and microvascular dilation to nifedipine is enhanced in the setting of coronary endothelial dysfunction, suggesting supersensitive dilator response. The association between microvascular response to nifedipine and endothelin levels in the coronary sinus needs further clarification.

Blood Flow Velocity↗

A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors.

We have recently reported that nicotine has angiogenic effects, which appear to be mediated through non-neuronal nicotinic acetylcholine receptors (nAChRs). Here, we describe the endogenous cholinergic pathway for angiogenesis. In an in vitro angiogenesis model, increasing concentrations of the nonselective nAChR antagonist mecamylamine completely and reversibly inhibited endothelial network formation. Although several nAChR isoforms are expressed on endothelial cells (ECs), a similar inhibition was only obtained with the selective alpha7-nAChR antagonist alpha-bungarotoxin, whereas other selective antagonists did not result in significant inhibition of network formation. alpha7-nAChR was upregulated during proliferation, by hypoxia in vitro, and by ischemia in vivo. The nAChR-induced network formation was partially dependent on VEGF, was completely dependent on the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, and finally resulted in NF-kappaB activation. In vivo, pharmacological inhibition of nAChR as well as genetic disruption of alpha7-nAChR expression significantly inhibited inflammatory angiogenesis and reduced ischemia-induced angiogenesis and tumor growth. Our results suggest that nAChRs may play an important role in physiological and pathological angiogenesis. To our knowledge, this is the first description of a cholinergic angiogenic pathway, and it suggests a novel avenue for therapeutic modulation of angiogenesis.

Animals↗