scholarly journals Towards Personalized Therapy of Aortic Stenosis

2021 ◽  
Vol 11 (12) ◽  
pp. 1292
Author(s):  
Piotr Mazur ◽  
Magdalena Kopytek ◽  
Michał Ząbczyk ◽  
Anetta Undas ◽  
Joanna Natorska
Keyword(s):  
Aortic Stenosis ◽  
Molecular Mechanisms ◽  
Randomized Trials ◽  
Current Knowledge ◽  
Lipid Lowering ◽  
Advanced Glycation ◽  
Calcific Aortic Stenosis ◽  
Treatment Pathways ◽  
Glycation End Products ◽  
Coagulation Proteins

Calcific aortic stenosis (CAS) is the most common cause of acquired valvular heart disease in adults with no available pharmacological treatment to inhibit the disease progression to date. This review provides an up-to-date overview of current knowledge of molecular mechanisms underlying CAS pathobiology and the related treatment pathways. Particular attention is paid to current randomized trials investigating medical treatment of CAS, including strategies based on lipid-lowering and antihypertensive therapies, phosphate and calcium metabolism, and novel therapeutic targets such as valvular oxidative stress, coagulation proteins, matrix metalloproteinases, and accumulation of advanced glycation end products.

scholarly journals Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Eva O. Melin ◽  
Jonatan Dereke ◽  
Magnus Hillman
Keyword(s):  
Type 1 Diabetes ◽  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Lipid Lowering ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Lipid Lowering Drugs ◽  
Glycation End Products ◽  
End Products

Abstract Background The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P <  0.001), and triglycerides (P <  0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

scholarly journals Molecular aspects of the pathological activation and differentiation of valvular interstitial cells during the development of calcific aortic stenosis

2019 ◽  
Vol 34 (3) ◽  
pp. 66-72
Author(s):  
A. E. Kostyunin
Keyword(s):  
Aortic Stenosis ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interstitial Cells ◽  
Valvular Interstitial Cells ◽  
Calcific Aortic Stenosis ◽  
Valve Tissue ◽  
Pathological Differentiation ◽  
Molecular Aspects ◽  
Atherosclerotic Process

Calcific aortic stenosis is the most common valvular heart disease. The pathogenesis of this disease is complex and resembles the atherosclerotic process in the blood vessels. It is known that valvular interstitial cell activation and subsequent differentiation into osteoblast- and myofibroblast-like cells is the main driving force of fibrous and calcified aortic valve tissue. However, the molecular mechanisms behind these processes are still not fully understood. Current information on this issue is collected and analyzed in this article. The main molecular pathways mediating the pathological differentiation of the valvular interstitial cells and the reasons for their activation are considered.

scholarly journals Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis

Glycobiology ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 2-18
Author(s):  
Ejazul Haque ◽  
Mohd Kamil ◽  
Adria Hasan ◽  
Safia Irfan ◽  
Saba Sheikh ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Advanced Glycation End Products ◽  
Cross Talk ◽  
Structural Changes ◽  
Current Knowledge ◽  
Normal Function ◽  
Protein Glycation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Abstract Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer. On the contrary, protein glycation is a cascade of irreversible nonenzymatic reaction of reducing sugar with the amino group of the protein resulting in the modification of protein structure and formation of advanced glycation end products (AGEs). These AGEs are reported to obstruct the normal function of proteins. Lately, it has been reported that protein aggregation occurs as a result of AGEs. This aggregation of protein promotes the transformation of healthy cells to neoplasia leading to tumorigenesis. In this review, we underline the current knowledge of protein aggregation and glycation along with the cross talk between the two, which may eventually lead to the development of cancer.

scholarly journals Role of Advanced Glycation End Products in Carcinogenesis and their Therapeutic Implications

2019 ◽  
Vol 24 (44) ◽  
pp. 5245-5251 ◽  
Author(s):  
David Schröter ◽  
Annika Höhn
Keyword(s):  
Advanced Glycation End Products ◽  
Molecular Mechanisms ◽  
The Body ◽  
Advanced Glycation ◽  
Therapeutic Implications ◽  
Age Related ◽  
Glycation End Products ◽  
End Products ◽  
Reduction Strategies

Aging is one of the biggest risk factors for the major prevalent diseases such as cardiovascular diseases, neurodegeneration and cancer, but due to the complex and multifactorial nature of the aging process, the molecular mechanisms underlying age-related diseases are not yet fully understood. Research has been intensive in the last years aiming to characterize the pathophysiology of aging and develop therapies to fight age-related diseases. In this context advanced glycation end products (AGEs) have received attention. AGEs, when accumulated in tissues, significantly increase the level of inflammation in the body which has long been associated with the development of cancer. Here we discuss the classical settings promoting AGE formation, as well as reduction strategies, occurrence and relevance of AGEs in cancer tissues and the role of AGE-interaction with the receptor for advanced glycation end products (RAGE) in cancer initiation and progression.

scholarly journals Advanced Glycation End Products Play Adverse Proinflammatory Activities in Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Roberta Sanguineti ◽  
Alessandra Puddu ◽  
François Mach ◽  
Fabrizio Montecucco ◽  
Giorgio Luciano Viviani
Keyword(s):  
Advanced Glycation End Products ◽  
Molecular Mechanisms ◽  
Systemic Circulation ◽  
Advanced Glycation ◽  
Public Health Burden ◽  
Glycation End Products ◽  
End Products ◽  
Cross Links ◽  
High Level ◽  
Global Population

Osteoporosis is a major public health burden that is expected to further increase as the global population ages. In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis. On the other hand, the gradual deterioration of the immune system during aging (defined as immunosenescence) is also characterized by the generation of a high level of oxidants and AGEs. The synthesis and accumulation of AGEs (both localized within the bone or in the systemic circulation) might trigger a vicious circle (in which inflammation and aging merged in the word “Inflammaging”) which can establish and sustain the development of osteoporosis. This narrative review will update the molecular mechanisms/pathways by which AGEs induce the functional and structural bone impairment typical of osteoporosis.

A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis

2005 ◽  
Vol 352 (23) ◽  
pp. 2389-2397 ◽  
Author(s):  
S. Joanna Cowell ◽  
David E. Newby ◽  
Robin J. Prescott ◽  
Peter Bloomfield ◽  
John Reid ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Randomized Trial ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Calcific Aortic Stenosis ◽  
Lowering Therapy

scholarly journals AGEs-Induced and Endoplasmic Reticulum Stress/Inflammation-Mediated Regulation of GLUT4 Expression and Atherogenesis in Diabetes Mellitus

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
Marisa Passarelli ◽  
Ubiratan Fabres Machado
Keyword(s):  
Diabetes Mellitus ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Glucose Transporter ◽  
Current Knowledge ◽  
Advanced Glycation ◽  
Inflammatory Stress ◽  
Glut4 Expression ◽  
Glycation End Products ◽  
Solute Carrier

In recent decades, complex and exquisite pathways involved in the endoplasmic reticulum (ER) and inflammatory stress responses have been demonstrated to participate in the development and progression of numerous diseases, among them diabetes mellitus (DM). In those pathways, several players participate in both, reflecting a complicated interplay between ER and inflammatory stress. In DM, ER and inflammatory stress are involved in both the pathogenesis of the loss of glycemic control and the development of degenerative complications. Furthermore, hyperglycemia increases the generation of advanced glycation end products (AGEs), which in turn refeed ER and inflammatory stress, contributing to worsening glycemic homeostasis and to accelerating the development of DM complications. In this review, we present the current knowledge regarding AGEs-induced and ER/inflammation-mediated regulation of the expression of GLUT4 (solute carrier family 2, facilitated glucose transporter member 4), as a marker of glycemic homeostasis and of cardiovascular disease (CVD) development/progression, as a leading cause of morbidity and mortality in DM.

scholarly journals Encapsulating Peritoneal Sclerosis (EPS): Analysis of Current Knowledge in the Literature and Observation of a Suspect Case

2020 ◽  
pp. 1-9
Author(s):  
Fabbri Nicolò ◽  
Fabbri Nicolò ◽  
S. Ferro
Keyword(s):  
Peritoneal Dialysis ◽  
Current Knowledge ◽  
Degradation Products ◽  
Pathological Process ◽  
Careful Monitoring ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
Single Kidney ◽  
Dialysis Solutions ◽  
Suspect Case

Among the medical complications of long-lasting Peritoneal Dialysis (PD) a particular pathology has been observed, the so-called Encapsulating Peritoneal Sclerosis (EPS). The main properties of the pathological process of EPS is represented by proliferative fibrosis and sclerosis of the peritoneum, which lead to the formation of the typical "cocoon" and obstruction. Since glucose, Advanced Glycation End products (AGEs), and Glucose Degradation Products (GDPs), are responsible for peritoneum fibrosis and sclerosis, biocompatible peritoneal dialysis solutions are recommended, with reduced quantities of AGEs and GDPs. Furthermore, careful monitoring of the patients is very important, especially after 5-8 years of PD. We performed an overview of the current literature available and discuss a “suspect” case of a 59-year-old male patient who underwent a single kidney transplant after a period of 8 year of peritoneal dialysis with numerous sub occlusive episodes, some of them required hospitalizations in a period between 2011 and 2019. Patient underwent to several radiologic exams for a suspect of a cocoon syndrome.

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