[Effects of atorvastatin on the proliferation and collagen synthesis of rat cardiac fibroblasts].
OBJECTIVE
To investigate the effects of atorvastatin on the proliferation and collagen synthesis of rat cardiac fibroblasts (CFs).


METHODS
Isolated and cultured CFs of neonatal Sprague-Dawley (SD) rats were isolated and cultured. The DNA synthesis of CFs was measured by (3)H-TdR uptake test. CFs proliferation was measured by thiazolyl blue (MTT) assay. Cell cycle distribution was determined with flow cytometer (FCM). Collagen synthesis was measured by 3H-proline uptake test.


RESULTS
(1) The (3)H-TdR uptake in the 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, and 10(-4) mol/L atorvastatin groups was (cpm/5,000 cells) 314 +/- 68, 253 +/- 52, 201 +/- 53, and 170 +/- 48 respectively, all significantly lower than that of the control group (378 +/- 65, all P < 0.001). (2) MTT colorimetry showed that the A(490) values were 0.288 +/- 0.008, 0.252 +/- 0.007, 0.225 +/- 0.008, and 0.216 +/- 0.013 respectively in the 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L and 10(-4) mol/L atorvastatin groups, all significantly lower than that in the control group (0.311 +/- 0.005, all P < 0.01). (3) The percentage of cells in G(0)/G(1) phase was 54.8% +/- 2.5%, 61.4% +/- 2.7%, 70.4% +/- 3.2%, and 82.0% +/- 4.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups, all significantly higher than that in the control group (46.5 +/- 2.9, all P < 0.01). The percentage of cells in S phase was 18.8% +/- 2.3%, 15.8% +/- 2.1%, 12.5% +/- 1.8%, and 7.3% +/- 2.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups, all significantly lower than that in the control group (23.1% +/- 2.0%, all P < 0.01). The percentage of cells in G(2)/M phase was 26.5% +/- 0.8%, 22.8% +/- 1.2%, 17.2% +/- 1.4%, and 10.7% +/- 2.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups respectively, all significantly lower than that in the control group (30.5% +/- 1.4%, all P < 0.01). The proliferation index (PI) was 45.3% +/- 2.5%, 38.6% +/- 2.7%, 29.6% +/- 3.2%, and 18.0% +/- 4.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups respectively, all significantly lower than that in the control group (53.5% +/- 2.9%, all P < 0.01). (4) The (3)H-proline uptake was (cpm/5 000 cells) 422 +/- 59, 332 +/- 67, 252 +/- 53, and 184 +/- 48 in the 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, and 10(-4) mol/L atorvastatin groups respectively, all significantly lower than that in the control group (566 +/- 62, all P < 0.01).


CONCLUSIONS
Atorvastatin inhibits effectively the proliferation of cultured rat CFs and the collagen synthesis therein, which may play a role in the regression of heart remodeling.
Tian
Jian-wei
JW
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Zhao
Lian-you
LY
Wang
Shi-wen
SW
Zhang
Hai-tao
HT
Zheng
Qiang-sun
QS
Yang
Xue-dong
XD
Xu
Lin
L
Fan
Yan-hong
YH
D000818:Animals; D000831:Animals, Newborn; D000069059:Atorvastatin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D003094:Collagen; D000069059:Atorvastatin