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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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Inflammatory cells in carotid atherosclerotic plaques studied by immunohistochemistry. Consecutive sections were stained for macrophages (A and C) and T-cells (B and D) on the plaque. Marked reductions in the number of positive cells within the intimae were observed in the nondiabetic group vs. the diabetic group both for macrophages (C) and T-cells (D). E: Macrophages. F: T-lymphocytes. *P < 0.05.
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Figure 4: Inflammatory cells in carotid atherosclerotic plaques studied by immunohistochemistry. Consecutive sections were stained for macrophages (A and C) and T-cells (B and D) on the plaque. Marked reductions in the number of positive cells within the intimae were observed in the nondiabetic group vs. the diabetic group both for macrophages (C) and T-cells (D). E: Macrophages. F: T-lymphocytes. *P < 0.05.

Mentions: In relation to nondiabetic atherosclerotic samples, the diabetic group showed a significant increase of the percentage of neointima staining positive for macrophages (22 ± 3 vs. 15 ± 3%; P < 0.05) (Fig. 4A and C) and T-cells (4.4 ± 2 vs. 1.8 ± 0.5%; P < 0.05) (Fig. 4B and D), which is consistent with the increased chemokine expression. Those results are similar to those found in the literature (25).


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)

Inflammatory cells in carotid atherosclerotic plaques studied by immunohistochemistry. Consecutive sections were stained for macrophages (A and C) and T-cells (B and D) on the plaque. Marked reductions in the number of positive cells within the intimae were observed in the nondiabetic group vs. the diabetic group both for macrophages (C) and T-cells (D). E: Macrophages. F: T-lymphocytes. *P < 0.05.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: Inflammatory cells in carotid atherosclerotic plaques studied by immunohistochemistry. Consecutive sections were stained for macrophages (A and C) and T-cells (B and D) on the plaque. Marked reductions in the number of positive cells within the intimae were observed in the nondiabetic group vs. the diabetic group both for macrophages (C) and T-cells (D). E: Macrophages. F: T-lymphocytes. *P < 0.05.
Mentions: In relation to nondiabetic atherosclerotic samples, the diabetic group showed a significant increase of the percentage of neointima staining positive for macrophages (22 ± 3 vs. 15 ± 3%; P < 0.05) (Fig. 4A and C) and T-cells (4.4 ± 2 vs. 1.8 ± 0.5%; P < 0.05) (Fig. 4B and D), which is consistent with the increased chemokine expression. Those results are similar to those found in the literature (25).

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