Biomedical subjects

S Soumian

Publications and source records attributed to S Soumian.

4 recordsLinked to original sources

PubMed2006

Placental ABCA1 expression is reduced in primary antiphospholipid syndrome compared to pre-eclampsia and controls.

The ATP binding cassette transporter A1 (ABCA1) mediates cellular cholesterol and phospholipid efflux, and is implicated in phosphatidylserine translocation and apoptosis. Loss of functional ABCA1 in null mice results in severe placental malformation. This study aimed to establish the placental localisation of ABCA1 and to investigate whether ABCA1 expression is altered in placentas from pregnancies complicated by pre-eclampsia and antiphospholipid syndrome. ABCA1 mRNA and protein localisation studies were carried out using in situ hybridization and immunohistochemistry. Comparisons of gene expression were performed using real-time PCR and immunoblotting. ABCA1 mRNA and protein was localised to the apical syncytium of placental villi and endothelia of fetal blood vessels within the villi. ABCA1 mRNA expression was reduced in placentas from women with APS when compared to controls (p<0.001), and this was paralleled by reductions in ABCA1 protein expression. There were no differences in ABCA1 expression between placentas from pre-eclamptic pregnancies and controls. The localisation of ABCA1 in human placenta is consistent with a role in cholesterol and phospholipid transport. The decrease in ABCA1 protein in APS may reflect reduced cholesterol transport to the fetus affecting the formation of cell membranes and decreasing the level of substrate available for steroidogenesis.

ATP Binding Cassette Transporter 1↗

PubMed2005

mRNA expression of genes involved in lipid efflux and matrix degradation in occlusive and ectatic atherosclerotic disease.

BACKGROUND: Atherosclerotic plaque behaviour is influenced by intra-plaque inflammation, matrix turnover, and the lipid core volume. Peroxisome proliferator activated receptor gamma (PPARgamma) modulates atherosclerosis by its anti-inflammatory and anti-protease activity. PPARgamma promotes lipid efflux through the liver X receptor alpha (LXRalpha) and the ATP binding cassette transporter A1 (ABCA1). Matrix metalloproteinase 9 (MMP-9) and cyclooxygenase 2 (COX-2) are implicated in plaque instability. AIMS: To assess the expression of these genes in occlusive and ectatic atherosclerotic disease to determine the relation between genes involved in lipid efflux and matrix degradation. METHODS: Carotid endarterectomy specimens from 16 patients and aneurysm tissue from 16 patients undergoing abdominal aortic aneurysm repair were used. Inferior mesenteric arteries from colectomy specimens from 12 patients served as controls. Total RNA was extracted from pulverised tissue and reverse transcribed into cDNA. Quantitative real time polymerase chain reaction (PCR) was performed using fluorescently labelled probes for ABCA1, LXRalpha, PPARgamma, COX-2, and MMP-9. RESULTS: PPARgamma expression was significantly lower in both occlusive and ecstatic atherosclerotic disease (p<0.001), whereas LXRalpha and ABCA1 expression was significantly increased (p<0.01). MMP-9 expression was significantly increased in diseased tissues (p<0.0001), and values were highest in occlusive disease (p<0.01). The increases in ABCA1 and MMP-9 mRNA were significantly correlated in diseased tissues (p<0.01, r=0.71 and r=0.78). COX-2 expression was increased in ectatic but low in occlusive disease (p<0.01). CONCLUSION: This observational study suggests a role for therapeutic upregulation of PPARgamma, which could potentially upregulate lipid efflux through ABCA1 and inhibit matrix degradation through inhibition of MMP-9.

ATP Binding Cassette Transporter 1↗

PubMed2005

ABCA1 and atherosclerosis.

ATP binding cassette transporter A1 (ABCA1) mediates the cellular efflux of phospholipids and cholesterol to lipid-poor apolipoprotein A1 (apoA1) and plays a significant role in high density lipoprotein (HDL) metabolism. ABCA1's role in the causation of Tangier disease, characterized by absent HDL and premature atherosclerosis, has implicated this transporter and its regulators liver-X-receptoralpha (LXRalpha) and peroxisome proliferator activated receptorgamma (PPARgamma) as new candidates potentially influencing the progression of atherosclerosis. In addition to lipid regulation, these genes are involved in apoptosis and inflammation, processes thought to be central to atherosclerotic plaque progression. A Medline-based review of the literature was carried out. Tangier disease and human heterozygotes with ABCA1 mutations provide good evidence that ABCA1 is a major candidate influencing atherosclerosis. Animal and in vitro experiments suggest that ABCA1 not only mediates cholesterol and phospholipid efflux, but is also involved in the regulation of apoptosis and inflammation. The complex and beneficial interactions between apoA1 and ABCA1 seem to be pivotal for cholesterol efflux. The expression of the ABCA1 is tightly regulated. Furthermore the plaque microenvironment could potentially promote ABCA1 protein degradation thus compromising cholesterol efflux. PPAR-LXR-ABCA1 interactions are integral to cholesterol homeostasis and these nuclear receptors have proven anti-inflammatory and anti-matrix metalloproteinase activity. Therapeutic manipulation of the ABCA1 transporter is feasible using PPAR and LXR agonists. PPAR agonists like glitazones and ABCA1 protein stabilization could potentially modify the clinical progression of atherosclerotic lesions.

ATP Binding Cassette Transporter 1↗

PubMed2004

ABCA1 expression in carotid atherosclerotic plaques.

BACKGROUND AND PURPOSE: The ATP-binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux from cells, a key process in reverse cholesterol transport. Whereas previous investigations focused on mutations causing impaired ABCA1 function, we assessed the role of ABCA1 in human carotid atherosclerotic disease. METHODS: We compared the mRNA and protein levels of ABCA1, and one of its key regulators, the liver X receptor alpha (LXRalpha), between minimally and grossly atherosclerotic arterial tissue. We established ABCA1 and LXRalpha gene expression by real-time quantitative polymerase chain reaction in 10 control and 18 atherosclerotic specimens. Presence of ABCA1 protein was assessed by immunoblotting. To determine whether differences observed at a local level were reflected in the systemic circulation, we measured ABCA1 mRNA in leukocytes of 10 patients undergoing carotid endarterectomy and 10 controls without phenotypic atherosclerosis. RESULTS: ABCA1 and LXRalpha gene expression were significantly elevated in atherosclerotic plaques (P<0.0001 and 0.03, respectively). The increased mRNA levels of ABCA1 and LXRalpha were correlated in atherosclerotic tissue (r=0.85; P<0.0001). ABCA1 protein expression was significantly reduced in plaques compared with control tissues (P<0.0001). There were no differences in leukocyte ABCA1 mRNA expression (P=0.67). CONCLUSIONS: ABCA1 gene and protein are expressed in minimally atherosclerotic human arteries. Despite significant upregulation of ABCA1 mRNA, possibly mediated via LXRalpha, ABCA1 protein is markedly reduced in advanced carotid atherosclerotic lesions. No differences in leukocyte ABCA1 expression were found, suggesting the plaque microenvironment may contribute to the differential ABCA1 expression. We propose that the decreased level of ABCA1 protein is a key factor in the development of atherosclerotic lesions.

ATP Binding Cassette Transporter 1↗