Limits...
Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes in human coronary artery smooth muscle cells.

Minta J, Jungwon Yun J, St Bernard R - Cell Biol Int Rep (2010) (2010)

Bottom Line: To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips.Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed.Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto M5S 1A8, Canada.

ABSTRACT
Recent studies suggest that circulating LDL (low-density lipoproteins) play a central role in the pathogenesis of atherosclerosis, and the oxidized form (ox-LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell formation and the transition of quiescent and contractile vascular SMCs (smooth muscle cells) to the migratory and proliferative phenotype. SMC phenotype transition and hyperplasia are the pivotal events in the pathogenesis of atherosclerosis. To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips. Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed. Our data suggests that the interaction of ox-LDL with its cognate receptors on SMCs modulates the induction of several growth factors and cytokines, which activate a variety of intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine, Rho kinase pathways) that contribute to SMC transition from the quiescent and contractile phenotype to the proliferative and migratory phenotype. Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

No MeSH data available.


Related in: MedlinePlus

Effect of n (normal) and ox (oxidized) LDL (2 μg/ml) on the proliferation of human coronary artery SMCs
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475437&req=5

Figure 1: Effect of n (normal) and ox (oxidized) LDL (2 μg/ml) on the proliferation of human coronary artery SMCs

Mentions: Confluent cultures of human coronary artery SMC were grown in the presence of 0.5% FBS for 48 h to induce quiescence. The cultures were then exposed to 2 μg/ml n-LDL or ox-LDL. The culture medium was replaced at day 2, and the cells were detached at day 5 to assess proliferation by cell counts. The mean and S.E.M. were determined for three separate experiments, each performed in quadruplicate. The increase in cell number in cultures containing n-LDL was only 1.3-fold greater than in cells cultured in the presence of 0.5% FBS. However, in the presence of ox-LDL, SMC proliferation was increased 3.1-fold relative to cells grown in 0.5% FBS alone (Figure 1).


Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes in human coronary artery smooth muscle cells.

Minta J, Jungwon Yun J, St Bernard R - Cell Biol Int Rep (2010) (2010)

Effect of n (normal) and ox (oxidized) LDL (2 μg/ml) on the proliferation of human coronary artery SMCs
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475437&req=5

Figure 1: Effect of n (normal) and ox (oxidized) LDL (2 μg/ml) on the proliferation of human coronary artery SMCs
Mentions: Confluent cultures of human coronary artery SMC were grown in the presence of 0.5% FBS for 48 h to induce quiescence. The cultures were then exposed to 2 μg/ml n-LDL or ox-LDL. The culture medium was replaced at day 2, and the cells were detached at day 5 to assess proliferation by cell counts. The mean and S.E.M. were determined for three separate experiments, each performed in quadruplicate. The increase in cell number in cultures containing n-LDL was only 1.3-fold greater than in cells cultured in the presence of 0.5% FBS. However, in the presence of ox-LDL, SMC proliferation was increased 3.1-fold relative to cells grown in 0.5% FBS alone (Figure 1).

Bottom Line: To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips.Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed.Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto M5S 1A8, Canada.

ABSTRACT
Recent studies suggest that circulating LDL (low-density lipoproteins) play a central role in the pathogenesis of atherosclerosis, and the oxidized form (ox-LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell formation and the transition of quiescent and contractile vascular SMCs (smooth muscle cells) to the migratory and proliferative phenotype. SMC phenotype transition and hyperplasia are the pivotal events in the pathogenesis of atherosclerosis. To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips. Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed. Our data suggests that the interaction of ox-LDL with its cognate receptors on SMCs modulates the induction of several growth factors and cytokines, which activate a variety of intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine, Rho kinase pathways) that contribute to SMC transition from the quiescent and contractile phenotype to the proliferative and migratory phenotype. Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

No MeSH data available.


Related in: MedlinePlus