The cardiovascular complications of diabetes: a striking link through protein glycation

Ahmad, Mousa Numan; Farah, A; Al-Qirim, Tareq

doi:10.2478/rjim-2020-0021

Cited by 17 publications

(14 citation statements)

References 61 publications

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“…This may be proceeded by the glycation process of proteins with its outcome as glycation end products, which present oxidative and proinflammatory effect [ 58 ]. Advanced glycation end products formed after a non-enzymatic reaction between monosaccharides and free amino groups of proteins, lipids, and nucleic acids are responsible for a cascade of inflammation, oxidative stress, and disruption of calcium homeostasis [ 59 ]. The second factor affecting free amino groups is platelet count.…”

Section: Discussionmentioning

confidence: 99%

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

et al. 2022

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Pathogenesis of cardiovascular diseases is caused by, inter alia, oxidative stress. On the other hand, cardiovascular risk factors may cause redox imbalance. The pathological pathways between those components are to be determined. In the group comprised of 300 sex-matched subjects, we evaluated a number of cardiovascular risk factors: blood pressure, body mass, lipids, glucose, homocysteine, uric acid, von Willebrand factor (vWF), VCAM-1 and ICAM-1. The presence of cardiovascular diseases and drugs for their treatment were examined. Secondly, we assessed total antioxidative status (TAS), total oxidative status (TOS) and other markers of oxidative stress. TAS was inversely related to LDL cholesterol. TOS was positively associated with BMI and female sex, but negatively associated with the use of angiotensin II receptor antagonists. Plasma lipid peroxides concentration was positively related to ICAM-1 and presence of stroke, whereas platelet lipid peroxides were positively associated with vWF. Platelets proteins thiol groups were in a positive relationship with vWF, but in a negative relationship with uric acid and diagnosed lipid disorders. Both free thiol and amino groups were positively associated with plasma glucose. Platelets free amino groups were related to platelets count. Superoxide generation by blood platelets (both with and without homocysteine) was positively connected to glucose level. Among women, oxidative markers appear to be more related to glucose level, whereas among men they are related to body mass indices. TAS, TOS and oxidative markers are largely related to modifiable cardiovascular risk factors such as body mass, and intake of drugs such as angiotensin II receptor blockers. Plasma and platelet oxidation markers appear to be especially associated with glucose concentration. The presented analyses unanimously indicate strong connections between cardiovascular risk factors and redox potential and specify how cardiometabolic interventions may counter-balance oxidative stress.

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Section: Discussionmentioning

confidence: 99%

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

et al. 2022

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“…The results showed that the levels of anti-AGE EL IgG antibodies were significantly higher in the T2D group compared to the control group, while the levels of anti-AGE EL IgM antibodies were similar to those in the controls ( Figure 1 ). The non-enzymatic glycation of vascular EL is a spontaneous process [ 32 ] that leads to the formation of autoantibodies against epitopes of AGE EL [ 29 ], both in normal aging and in diabetes [ 33 ]. The IgM class of autoantibodies predominates in the early stage of the immune response and later undergoes switching to the IgG class, which has the same antigen specificity [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression

Kostov

Blazhev

2022

Pathophysiology

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The increased glycation of elastin is an important factor in vascular changes in diabetes. Using the ELISA method, we determined serum levels of IgM and IgG autoantibodies to advanced glycation end products of vascular elastin (anti-AGE EL IgM and anti-AGE EL IgG) in 59 hypertensive patients with type 2 diabetes (T2D) and 20 healthy controls. Serum levels of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and the C-reactive protein (CRP) were also determined. The levels of anti-AGE EL IgM antibodies in the T2D group were similar to those in the control group, while those of anti-AGE EL IgG antibodies were significantly higher (p = 0.017). Significant positive correlations were found between the levels of anti-AGE EL IgM antibodies and MMP-2 (r = 0.322; p = 0.013) and between the levels of anti-AGE EL IgG antibodies and CRP (r = 0.265; p = 0.042). Our study showed that elevated anti-AGE EL IgG antibody levels may be an indicator of the enhanced AGE-modification and inflammatory-mediated destruction of vascular elastin in hypertensive patients with T2D. Anti-AGE EL IgM antibodies may reflect changes in vascular MMP-2 activity, and their elevated levels may be a sign of early vascular damage.

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“…Recent reviews have also covered roles for AGEs/RAGE ligands and RAGE in the pathogenesis of diabetic complications [17,97,98]. Targeting RAGE for the prevention/treatment of diabetic complications, as well as other RAGE-related disorders, is the critical requirement for the discovery of RAGE's innate functions.…”

Section: Small Molecules Targeting the Cytoplasmic Domain Of Rage Int...mentioning

confidence: 99%

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

Ramasamy

Shekhtman

Schmidt

2022

IJMS

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Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand–receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues. Although successful targeting of RAGE in the clinical milieu has, to date, not been met with success, recent approaches to target RAGE intracellular signaling may hold promise to fill this critical gap. This review focuses on recent examples of highlights and updates to the pathobiology of RAGE and DIAPH1 in diabetic complications.

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The cardiovascular complications of diabetes: a striking link through protein glycation

Cited by 17 publications

References 61 publications

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

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