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Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis.

Giaginis C, Klonaris C, Katsargyris A, Kouraklis G, Spiliopoulou C, Theocharis S - Med. Sci. Monit. (2011)

Bottom Line: PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients.Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015).PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Medicine and Toxicology, University of Athens, Athens, Greece.

ABSTRACT

Background: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-gamma and RXR-alpha expression in different cellular populations localized within advanced carotid atherosclerosis lesions.

Material/methods: PPAR-gamma and RXR-alpha expression was assessed by immunohistochemistry in 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients' medical history, risk factors and medication intake.

Results: Increased incidence of low PPAR-gamma expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-alpha expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015).

Conclusions: PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

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Related in: MedlinePlus

Representative immunostainings for PPAR-γ in (A). Macrophages and (B). Smooth muscle cells (original magnification ×400).
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f1-medscimonit-17-7-cr381: Representative immunostainings for PPAR-γ in (A). Macrophages and (B). Smooth muscle cells (original magnification ×400).

Mentions: PPAR-γ positivity in macrophages and smooth muscle cells was noted in 84 (63%) and 95 (71%) out of 134 carotid specimens, respectively. RXR-α positivity in macrophages and smooth muscle cells was noted in 129 (96%) and 133 (99%) out of 134 carotid specimens, respectively. Representative immunostainings for PPAR-γ and RXR-α protein expression in macrophages and smooth muscle cells are depicted in Figures 1 and 2, respectively. The vast majority of carotid specimens did not show positive immunoreactivity for PPAR-γ and RXR-α in endothelial cells, as only 11 (8%) cases were PPAR-γ positive and only 13 (10%) cases were RXR-α positive (data not shown). The low incidence of PPAR-γ and RXR-α immunopositivity in endothelial cells did not permit any statistical analysis with clinical variables in this cellular population (data not shown).


Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis.

Giaginis C, Klonaris C, Katsargyris A, Kouraklis G, Spiliopoulou C, Theocharis S - Med. Sci. Monit. (2011)

Representative immunostainings for PPAR-γ in (A). Macrophages and (B). Smooth muscle cells (original magnification ×400).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539575&req=5

f1-medscimonit-17-7-cr381: Representative immunostainings for PPAR-γ in (A). Macrophages and (B). Smooth muscle cells (original magnification ×400).
Mentions: PPAR-γ positivity in macrophages and smooth muscle cells was noted in 84 (63%) and 95 (71%) out of 134 carotid specimens, respectively. RXR-α positivity in macrophages and smooth muscle cells was noted in 129 (96%) and 133 (99%) out of 134 carotid specimens, respectively. Representative immunostainings for PPAR-γ and RXR-α protein expression in macrophages and smooth muscle cells are depicted in Figures 1 and 2, respectively. The vast majority of carotid specimens did not show positive immunoreactivity for PPAR-γ and RXR-α in endothelial cells, as only 11 (8%) cases were PPAR-γ positive and only 13 (10%) cases were RXR-α positive (data not shown). The low incidence of PPAR-γ and RXR-α immunopositivity in endothelial cells did not permit any statistical analysis with clinical variables in this cellular population (data not shown).

Bottom Line: PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients.Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015).PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Medicine and Toxicology, University of Athens, Athens, Greece.

ABSTRACT

Background: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-gamma and RXR-alpha expression in different cellular populations localized within advanced carotid atherosclerosis lesions.

Material/methods: PPAR-gamma and RXR-alpha expression was assessed by immunohistochemistry in 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients' medical history, risk factors and medication intake.

Results: Increased incidence of low PPAR-gamma expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-alpha expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015).

Conclusions: PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

Show MeSH
Related in: MedlinePlus