The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells.
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 PPARgamma, 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.
Perez-Vizcaino
Francisco
F
Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, Queen Mary University of London, UK. fperez@med.ucm.es
Bishop-Bailley
David
D
Lodi
Federica
F
Duarte
Juan
J
Cogolludo
Angel
A
Moreno
Laura
L
Bosca
Lisardo
L
Mitchell
Jane A
JA
Warner
Timothy D
TD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology*
D008024:Ligands; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D011794:Quercetin; D048031:JNK Mitogen-Activated Protein Kinases