The early- and late stages in phenotypic modulation of vascular smooth muscle cells

Differential roles for lysophosphatidic acid

Huazhang Guo, Natalia Makarova, Yunhui Cheng, Rui Rui Ji, Chunxiang Zhang, Patricia Farrar, Gabor Tigyi

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) has been implicated as causative in phenotypic modulation (PM) of cultured vascular smooth muscle cells (VSMC) in their transition to the dedifferentiated phenotype. We evaluated the contribution of the three major LPA receptors, LPA1 and LPA2 GPCR and PPARγ, on PM of VSMC. Expression of differentiated VSMC-specific marker genes, including smooth muscle α-actin, smooth muscle myosin heavy chain, calponin, SM-22α, and h-caldesmon, was measured by quantitative real-time PCR in VSMC cultures and aortic rings kept in serum-free chemically defined medium or serum- or LPA-containing medium using wild-type C57BL/6, LPA1, LPA2, and LPA1&2 receptor knockout mice. Within hours after cells were deprived of physiological cues, the expression of VSMC marker genes, regardless of genotype, rapidly decreased. This early PM was neither prevented by IGF-I, inhibitors of p38, ERK1/2, or PPARγ nor significantly accelerated by LPA or serum. To elucidate the mechanism of PM in vivo, carotid artery ligation with/without replacement of blood with Krebs solution was used to evaluate contributions of blood flow and pressure. Early PM in the common carotid was induced by depressurization regardless of the presence/absence of blood, but eliminating blood flow while maintaining blood pressure or after sham surgery elicited no early PM. The present results indicate that LPA, serum, dissociation of VSMC, IGF-I, p38, ERK1/2, LPA1, and LPA2 are not causative factors of early PM of VSMC. Tensile stress generated by blood pressure may be the fundamental signal maintaining the fully differentiated phenotype of VSMC.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1781
Issue number9
DOIs
StatePublished - Sep 1 2008

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Vascular Smooth Muscle
Smooth Muscle Myocytes
Peroxisome Proliferator-Activated Receptors
Blood Pressure
Serum
Insulin-Like Growth Factor I
Lysophosphatidic Acid Receptors
Smooth Muscle Myosins
Calmodulin-Binding Proteins
Phenotype
Myosin Heavy Chains
lysophosphatidic acid
Carotid Arteries
Knockout Mice
Genes
Cues
Ligation
Smooth Muscle
Actins
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

The early- and late stages in phenotypic modulation of vascular smooth muscle cells : Differential roles for lysophosphatidic acid. / Guo, Huazhang; Makarova, Natalia; Cheng, Yunhui; Ji, Rui Rui; Zhang, Chunxiang; Farrar, Patricia; Tigyi, Gabor.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1781, No. 9, 01.09.2008, p. 571-581.

Research output: Contribution to journalReview article

Guo, Huazhang ; Makarova, Natalia ; Cheng, Yunhui ; Ji, Rui Rui ; Zhang, Chunxiang ; Farrar, Patricia ; Tigyi, Gabor. / The early- and late stages in phenotypic modulation of vascular smooth muscle cells : Differential roles for lysophosphatidic acid. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2008 ; Vol. 1781, No. 9. pp. 571-581.
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T2 - Differential roles for lysophosphatidic acid

AU - Guo, Huazhang

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AU - Cheng, Yunhui

AU - Ji, Rui Rui

AU - Zhang, Chunxiang

AU - Farrar, Patricia

AU - Tigyi, Gabor

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N2 - Lysophosphatidic acid (LPA) has been implicated as causative in phenotypic modulation (PM) of cultured vascular smooth muscle cells (VSMC) in their transition to the dedifferentiated phenotype. We evaluated the contribution of the three major LPA receptors, LPA1 and LPA2 GPCR and PPARγ, on PM of VSMC. Expression of differentiated VSMC-specific marker genes, including smooth muscle α-actin, smooth muscle myosin heavy chain, calponin, SM-22α, and h-caldesmon, was measured by quantitative real-time PCR in VSMC cultures and aortic rings kept in serum-free chemically defined medium or serum- or LPA-containing medium using wild-type C57BL/6, LPA1, LPA2, and LPA1&2 receptor knockout mice. Within hours after cells were deprived of physiological cues, the expression of VSMC marker genes, regardless of genotype, rapidly decreased. This early PM was neither prevented by IGF-I, inhibitors of p38, ERK1/2, or PPARγ nor significantly accelerated by LPA or serum. To elucidate the mechanism of PM in vivo, carotid artery ligation with/without replacement of blood with Krebs solution was used to evaluate contributions of blood flow and pressure. Early PM in the common carotid was induced by depressurization regardless of the presence/absence of blood, but eliminating blood flow while maintaining blood pressure or after sham surgery elicited no early PM. The present results indicate that LPA, serum, dissociation of VSMC, IGF-I, p38, ERK1/2, LPA1, and LPA2 are not causative factors of early PM of VSMC. Tensile stress generated by blood pressure may be the fundamental signal maintaining the fully differentiated phenotype of VSMC.

AB - Lysophosphatidic acid (LPA) has been implicated as causative in phenotypic modulation (PM) of cultured vascular smooth muscle cells (VSMC) in their transition to the dedifferentiated phenotype. We evaluated the contribution of the three major LPA receptors, LPA1 and LPA2 GPCR and PPARγ, on PM of VSMC. Expression of differentiated VSMC-specific marker genes, including smooth muscle α-actin, smooth muscle myosin heavy chain, calponin, SM-22α, and h-caldesmon, was measured by quantitative real-time PCR in VSMC cultures and aortic rings kept in serum-free chemically defined medium or serum- or LPA-containing medium using wild-type C57BL/6, LPA1, LPA2, and LPA1&2 receptor knockout mice. Within hours after cells were deprived of physiological cues, the expression of VSMC marker genes, regardless of genotype, rapidly decreased. This early PM was neither prevented by IGF-I, inhibitors of p38, ERK1/2, or PPARγ nor significantly accelerated by LPA or serum. To elucidate the mechanism of PM in vivo, carotid artery ligation with/without replacement of blood with Krebs solution was used to evaluate contributions of blood flow and pressure. Early PM in the common carotid was induced by depressurization regardless of the presence/absence of blood, but eliminating blood flow while maintaining blood pressure or after sham surgery elicited no early PM. The present results indicate that LPA, serum, dissociation of VSMC, IGF-I, p38, ERK1/2, LPA1, and LPA2 are not causative factors of early PM of VSMC. Tensile stress generated by blood pressure may be the fundamental signal maintaining the fully differentiated phenotype of VSMC.

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JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

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