Cigarette Smoke Extracts Promote Vascular Smooth Muscle Cell Proliferation and Enhances Contractile Responses in the Vasculature and Airway.

• Cigarette smoke exposure is a strong risk factor for cardiovascular and respiratory diseases. However, the knowledge about how cigarette smoke induces damage to vasculature and airway is limited. The present study was designed to examine the effects of cigarette smoke particles extracted by heptane (heptane-soluble smoke particles, HSP), by water (water-soluble smoke particles, WSP) and by DMSO (DMSO-soluble smoke particles, DSP), which represent lipophilic, hydrophilic and ambiphoteric constituents from the cigarette smoke, respectively. Human aortic smooth muscle cell (HASMC) proliferation was assessed in cell culture. Rat resistance artery and airway contractile responses to serotonin, U46619, phenylephrine, noradrenaline, acetylcholine, des-Arg(9)-bradykinin, bradykinin, sarafotoxin 6c and endothelin-1 were monitored by a sensitive myograph system. Immunocytochemistry and cell-based phosphoELISA assay were used to demonstrate activation of extracellular signal-regulated kinases 1/2 (ERK1/2). For the first time, our results demonstrate that although all the three extracts promote HASMC proliferation, the HSP and DSP effects occur earlier. HSP and DSP, but not WSP, increase the contractile responses to sarafotoxin 6c, U46619 or bradykinin in rat mesenteric artery and/or in bronchi. ERK1/2 is activated by HSP and DSP in HASMCs and inhibition of ERK1/2 abrogated the smoke extracts-induced HASMC proliferation, while blockage of nicotinic receptors had no effects, suggesting that the toxic effects of the smoke extracts occur via activation of intracellular ERK1/2 signalling, but not nicotinic receptors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)