Cyclic strain stimulates L-proline transport in vascular smooth muscle cells.
BACKGROUND
The increase in vessel wall strain in hypertension contributes to arterial remodeling by stimulating vascular smooth muscle cell (SMC) proliferation and collagen synthesis. Because L-proline is essential for the synthesis of collagen and cell growth, we examined whether cyclic strain regulates the transcellular transport of L-proline by vascular SMC.


METHODS
Cultured rat aortic SMCs were subjected to mechanical strain using the Flexercell 3000 Strain Unit.


RESULTS
Cyclic strain increased L-proline transport in a time- and strain-degree-dependent manner that was inhibited by cycloheximide or actinomycin D. Kinetic studies indicated that cyclic strain-induced L-proline uptake was mediated by an increase in transport capacity independent of any change in the affinity for L-proline. Cyclic strain stimulated the expression of system A amino acid transporter 2 mRNA in a time-dependent fashion that paralleled the increase in L-proline transport. Cyclic strain also induced the release of transforming growth factor-beta1 in a time- and strain-dependent manner. Moreover, conditioned media from SMCs exposed to cyclic strain stimulated the transport of L-proline in control, static SMCs and this was significantly attenuated by a transforming growth factor-beta1 neutralizing antibody.


CONCLUSIONS
These results demonstrate that cyclic strain stimulates L-proline transport by inducing system A amino acid transporter 2 gene expression through the autocrine release of transforming growth factor-beta1. The ability of cyclic strain to induce system A amino acid transporter 2 expression may promote arterial remodeling in hypertension by providing vascular SMCs with the necessary intracellular levels of L-proline required for collagen synthesis and cell growth.
Michael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
Sylvia V
SV
Reyna
Diana
D
Ensenat
Fruzsina K
FK
Johnson
Hong
H
Wang
Andrew I
AI
Schafer
William
W
Durante
D026924:Amino Acid Transport System A / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D019898:Autocrine Communication / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011392:Proline / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D026924:Amino Acid Transport System A; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011392:Proline