The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells

• Published in: Biochemical and biophysical research communications 2006-08, Vol.346 (3), p.919-925
• Main Authors: Perez-Vizcaino, Francisco, Bishop-Bailley, David, Lodi, Federica, Duarte, Juan, Cogolludo, Angel, Moreno, Laura, Bosca, Lisardo, Mitchell, Jane A., Warner, Timothy D.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; AORTA; APOPTOSIS; Apoptosis - drug effects; BLOOD PRESSURE; CAROTID ARTERIES; Cell Nucleus - drug effects; Cell Shape; Cells, Cultured; Enzyme Activation - drug effects; Flavonoid; Intimal; JNK; JNK Mitogen-Activated Protein Kinases - metabolism; Ligands; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; MUSCLES; NITRIC OXIDE; Nitric Oxide - biosynthesis; OXIDIZERS; PHOSPHORYLATION; Phosphorylation - drug effects; PPAR gamma - metabolism; QUERCETIN; Quercetin - pharmacology; RATS; Reactive Oxygen Species - metabolism; Tunica Intima - cytology; Vascular smooth muscle; VASODILATORS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.05.198

Quercetin, the most abundant dietary flavonol, exerts vasodilator, anti-hypertensive, and anti-atherogenic effects and reduces the vascular remodelling associated with elevated blood pressure. Here, we have compared the effects of quercetin in intimal- and medial-type rat vascular smooth muscle cells (VSMC) in culture. After 48 h, quercetin reduced the viability of a polyclonal intimal-type cell line derived from neonatal aorta but not of a medial-type cell line derived from adult aorta. These differential effects were similar in both proliferating and quiescent VSMC. Quercetin also preferentially reduced the viability of intimal-type over medial-type VSMC in primary cultures derived from balloon-injured carotid arteries. The effects of quercetin on cell viability were mainly dependent upon induction of apoptosis, as demonstrated by nuclear condensation and fragmentation, and were unrelated to PPARγ, pro-oxidant effects or nitric oxide. The expression of MAPKs (ERK, p38, and JNK) and ERK phosphorylation were not different between intimal- and medial-type VSMC. p38 phosphorylation was negligible in both cell types. Medial-type showed a weak JNK phosphorylation while this was markedly increased in intimal-type cells. Quercetin reduced JNK phosphorylation but had no consistent effect on ERK phosphorylation. In conclusion, quercetin preferentially produced apoptosis in intimal-type compared to medial-type VSMC. This might play a role in the anti-atherogenic and anti-hypertensive effects of quercetin.