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Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

Mas S, Martínez-Pinna R, Martín-Ventura JL, Pérez R, Gomez-Garre D, Ortiz A, Fernandez-Cruz A, Vivanco F, Egido J - Diabetes (2010)

Bottom Line: Higher levels of NEFA were also found in diabetic sera.Finally, linoleic acid activates NF-kappaB and upregulates NF-kappaB-mediated LPL and MCP-1 expression in cultured VSMC.We hypothesize that NEFA may be produced locally and contribute to local inflammation.

View Article: PubMed Central - PubMed

Affiliation: Vascular Pathology and Experimental Nephrology Laboratory, Fundación Jiménez Díaz/Autonoma University/IRSIN, Madrid, Spain. smas@fjd.es

ABSTRACT

Objective: Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity.

Research design and methods: Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for metabolomic analysis imaging of frozen carotid atheroma plaques. Carotid endarterectomy specimens were used for conventional immunohistochemistry, laser-capture microdissection quantitative PCR, and in situ Southwestern hybridization. Biological actions of linoleic acid were studied in cultured vascular smooth muscle cells (VSMCs).

Results: TOF-SIMS imaging evidenced a significant increase in the quantity of several NEFA in diabetic versus nondiabetic atheroma plaques. Higher levels of NEFA were also found in diabetic sera. The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA. The pattern of distribution of plaque NEFA is similar to that of MCP-1, LPL, and activated NF-kappaB. Diabetic endarterectomy specimens showed higher numbers of infiltrating macrophages and T-lymphocytes-a finding that associated with higher NEFA levels. Finally, linoleic acid activates NF-kappaB and upregulates NF-kappaB-mediated LPL and MCP-1 expression in cultured VSMC.

Discussion: There is an increased presence of NEFA in diabetic plaque neointima. NEFA levels are higher in diabetic atheroma plaques than in nondiabetic subjects. We hypothesize that NEFA may be produced locally and contribute to local inflammation.

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Related in: MedlinePlus

Representative secondary ion images obtained from carotid endarteries obtained from a nondiabetic suject (top panel) and a diabetic subject (bottom panel) under the irradiation of bismuth cluster ions. From left to right: tissue micrograph (A); palmitate (C16:0) (B); palmitoleate (C16:1) (C); stearate (C18:0) (D); oleate (C18:1) (E); linoleate (C18:2) (F); image overlay of palmiteleate (red), cholesterol (green), and triglycerides (blue) (G); phosphate (H), phosphoinositol fragment (I), triglycerides (J), cholesterol (K), and total ion intensity (L). The field of view is 8 × 8 mm at 15,625 μm/pixel. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 1: Representative secondary ion images obtained from carotid endarteries obtained from a nondiabetic suject (top panel) and a diabetic subject (bottom panel) under the irradiation of bismuth cluster ions. From left to right: tissue micrograph (A); palmitate (C16:0) (B); palmitoleate (C16:1) (C); stearate (C18:0) (D); oleate (C18:1) (E); linoleate (C18:2) (F); image overlay of palmiteleate (red), cholesterol (green), and triglycerides (blue) (G); phosphate (H), phosphoinositol fragment (I), triglycerides (J), cholesterol (K), and total ion intensity (L). The field of view is 8 × 8 mm at 15,625 μm/pixel. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: Atheroma plaque samples subjected to TOF-SIMS imaging analysis using bismuth clusters as the primary ion source render multiple secondary ions corresponding with some of the most abundant metabolites present on their surface (Fig. 1). Ionization using liquid ion guns is biased toward more hydrophobic metabolites rendering secondary ions. Therefore, we focused on surface analysis of lipids and lipid derivatives.


Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

Mas S, Martínez-Pinna R, Martín-Ventura JL, Pérez R, Gomez-Garre D, Ortiz A, Fernandez-Cruz A, Vivanco F, Egido J - Diabetes (2010)

Representative secondary ion images obtained from carotid endarteries obtained from a nondiabetic suject (top panel) and a diabetic subject (bottom panel) under the irradiation of bismuth cluster ions. From left to right: tissue micrograph (A); palmitate (C16:0) (B); palmitoleate (C16:1) (C); stearate (C18:0) (D); oleate (C18:1) (E); linoleate (C18:2) (F); image overlay of palmiteleate (red), cholesterol (green), and triglycerides (blue) (G); phosphate (H), phosphoinositol fragment (I), triglycerides (J), cholesterol (K), and total ion intensity (L). The field of view is 8 × 8 mm at 15,625 μm/pixel. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874689&req=5

Figure 1: Representative secondary ion images obtained from carotid endarteries obtained from a nondiabetic suject (top panel) and a diabetic subject (bottom panel) under the irradiation of bismuth cluster ions. From left to right: tissue micrograph (A); palmitate (C16:0) (B); palmitoleate (C16:1) (C); stearate (C18:0) (D); oleate (C18:1) (E); linoleate (C18:2) (F); image overlay of palmiteleate (red), cholesterol (green), and triglycerides (blue) (G); phosphate (H), phosphoinositol fragment (I), triglycerides (J), cholesterol (K), and total ion intensity (L). The field of view is 8 × 8 mm at 15,625 μm/pixel. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: Atheroma plaque samples subjected to TOF-SIMS imaging analysis using bismuth clusters as the primary ion source render multiple secondary ions corresponding with some of the most abundant metabolites present on their surface (Fig. 1). Ionization using liquid ion guns is biased toward more hydrophobic metabolites rendering secondary ions. Therefore, we focused on surface analysis of lipids and lipid derivatives.

Bottom Line: Higher levels of NEFA were also found in diabetic sera.Finally, linoleic acid activates NF-kappaB and upregulates NF-kappaB-mediated LPL and MCP-1 expression in cultured VSMC.We hypothesize that NEFA may be produced locally and contribute to local inflammation.

View Article: PubMed Central - PubMed

Affiliation: Vascular Pathology and Experimental Nephrology Laboratory, Fundación Jiménez Díaz/Autonoma University/IRSIN, Madrid, Spain. smas@fjd.es

ABSTRACT

Objective: Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity.

Research design and methods: Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for metabolomic analysis imaging of frozen carotid atheroma plaques. Carotid endarterectomy specimens were used for conventional immunohistochemistry, laser-capture microdissection quantitative PCR, and in situ Southwestern hybridization. Biological actions of linoleic acid were studied in cultured vascular smooth muscle cells (VSMCs).

Results: TOF-SIMS imaging evidenced a significant increase in the quantity of several NEFA in diabetic versus nondiabetic atheroma plaques. Higher levels of NEFA were also found in diabetic sera. The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA. The pattern of distribution of plaque NEFA is similar to that of MCP-1, LPL, and activated NF-kappaB. Diabetic endarterectomy specimens showed higher numbers of infiltrating macrophages and T-lymphocytes-a finding that associated with higher NEFA levels. Finally, linoleic acid activates NF-kappaB and upregulates NF-kappaB-mediated LPL and MCP-1 expression in cultured VSMC.

Discussion: There is an increased presence of NEFA in diabetic plaque neointima. NEFA levels are higher in diabetic atheroma plaques than in nondiabetic subjects. We hypothesize that NEFA may be produced locally and contribute to local inflammation.

Show MeSH
Related in: MedlinePlus