Molecular mechanism of green microalgae, Dunaliella salina, involved in attenuating balloon injury-induced neointimal formation.
The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMC). The preventive effects of ethanol extract of Dunaliella salina (EDS) on balloon injury-induced neointimal formation were investigated. To explore its molecular mechanism in regulating cell proliferation, we first showed that EDS markedly reduced the human aortic smooth muscle cell proliferation via the inhibition of 5'-bromo-2'-deoxyuridine (BrdU) incorporation at 40 and 80 microg/ml. This was further supported by the G0/G1-phase arrest using a flow cytometric analysis. In an in vivo study, EDS at 40 and 80 microg/ml was previously administered to the Sprague-Dawley rats and found that the thickness of neointima, and the ratio of neointima:media were also reduced. EDS inhibited VSMC proliferation in a dose-dependent manner following stimulation of VSMC cultures with 15 % fetal bovine serum (FBS). Suppressed by EDS were 15 % FBS-stimulated intracellular Raf, phosphorylated extracellular signal-regulated kinases (p-Erk) involved in cell-cycle arrest and proliferating cell nuclear antigen. Phosphorylated focal adhesion kinase (p-FAK) was also suppressed by EDS. Also active caspase-9, caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels were increased by administration with EDS; the apoptotic pathway may play an important role in the regulatory effects of EDS on cell growth. These observations provide a mechanism of EDS in attenuating cell proliferation, thus as a potential intervention for restenosis.
Sheu
Ming-Jyh
MJ
School of Pharmacy, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan. soybean13mtdtw@gmail.com
Cheng
Hsu-Chen
HC
Chien
Yi-Chung
YC
Chou
Pei-Yu
PY
Huang
Guang-Jhong
GJ
Chen
Jwo-Sheng
JS
Lin
Sung-Yuan
SY
Wu
Chieh-Hsi
CH
D000800:Angioplasty, Balloon; D000818:Animals; D001011:Aorta / Q000293:injuries; D001973:Bromodeoxyuridine / Q000037:antagonists & inhibitors; D002317:Cardiovascular Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D000460:Chlorophyta; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007399:Interphase; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002317:Cardiovascular Agents; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D011064:Poly Adenosine Diphosphate Ribose; D053148:Caspase 3; D053453:Caspase 9; D001973:Bromodeoxyuridine