scholarly journals ApoD and ApoA-IV, novel proteomic components in HDL of diabetic kidney disease without dialysis

2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D (apoD) and apoA-IV. HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Monique F. M. Santana ◽  
Aécio L. A. Lira ◽  
Raphael S. Pinto ◽  
Carlos A. Minanni ◽  
Amanda R. M. Silva ◽  
...  

Abstract Background and aims Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods Individuals with DKD were divided into eGFR> 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and eGFR< 60 plus A3 (n = 25) and matched by age with control subjects (eGFR> 60; n = 8). Results Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR< 60 + A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR< 60 + A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR< 60 + A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular ( CVD ) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m 2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D ( apoD ) and apoA-IV . HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14 C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: Individuals with DKD were divided into eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR<60+A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR<60+A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR<60+A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion: The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: Individuals with DKD were divided into eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR<60+A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR<60+A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR<60+A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion: The increase in apoD and apoA-IV seems to counteract the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetes mellitus kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CV) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CV complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to glomerular filtration rate (GFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in GFR > 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and GFR < 60 plus A3 (n = 25) and matched by age with control subjects (GFR > 60; n = 8). Results: Targeted proteomic analyses quantified 29 proteins associated with HDL in all groups, although only 2 were more expressed in GFR < 60 + A3 group in comparison to controls: apolipoprotein D (apo D) and apo A-IV. HDL from GFR < 60 + A3 presented higher levels of total AGEs, pentosidine and carbamoylation (1.2, 1.1 and 4.2 times, respectively) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from GFR < 60 + A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in apo A-IV that presents many antiatherogenic actions seems to counteract the HDL chemical modification by AGE and carbamoylation and its increment in apo D that occurred in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: Individuals with DKD were divided into eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR<60+A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR<60+A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR<60+A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion: The increase in apoD and apoA-IV seems to counteract the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.


2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  

Abstract Background and aims:Diabetes mellitus kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CV) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CV complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to glomerular filtration rate (GFR) and urinary albumin excretion rate (AER).Methods:DKD individuals were divided in GFR > 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and GFR < 60 plus A3 (n = 25) and matched by age with control subjects (GFR > 60; n = 8).Results:Targeted proteomic analyses quantified 29 proteins associated with HDL in all groups, although only 2 were more expressed in GFR < 60 + A3 group in comparison to controls: apolipoprotein D (apo D) and apo A-IV. HDL from GFR < 60 + A3 presented higher levels of total AGEs, pentosidine and carbamoylation (1.2, 1.1 and 4.2 times, respectively) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from GFR < 60 + A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group.Conclusion:The increment in apo A-IV that presents many antiatherogenic actions seems to counteract the HDL chemical modification by AGE and carbamoylation and its increment in apo D that occurred in well-established DKD.


2018 ◽  
Vol 5 (6) ◽  
pp. 171871 ◽  
Author(s):  
Xin-Ge Yue ◽  
Zai-Gang Yang ◽  
Yue Zhang ◽  
Gui-Jun Qin ◽  
Fei Liu

To investigate the correlations between SIRT1 gene polymorphisms and diabetic kidney disease (DKD). There were 150 patients with DKD in the observation group (urinary albumin excretion rate (UAER) ≥ 300 mg 24 h −1 ), and 160 patients with a more than 10 year history of type 2 diabetes but without retinopathy and DKD (UAER < 30 mg 24 h −1 ) in the control group. Genotypes of three tagged single-nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1 gene in the two groups were detected. Risks of DKD for patients with the GG and GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92 times higher than that for AA genotype carriers, respectively. The risk of DKD for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21 times higher than that for AA and for AA + AG genotype carriers, respectively, and the risk of DKD for patients with allele G was 0.66 times higher than that for allele A carriers. There was no significant difference in genotype frequency of rs4746720 locus gene polymorphisms between the observation and control groups. The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype GG and allele G in the rs3818292 locus can decrease the risk of DKD.


2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199252
Author(s):  
Yuwei Yang ◽  
Peng Xu ◽  
Yan Liu ◽  
Xiaohong Chen ◽  
Yiyang He ◽  
...  

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.


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