scholarly journals Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Clément Mercier ◽  
Marina Rousseau ◽  
Pedro Geraldes
Keyword(s):  
Growth Factor ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Protein Tyrosine ◽  
Collateral Arteries ◽  
Increased Risk ◽  
Artery Disease

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Baseline Serum ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72).Conclusions: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Baseline Serum ◽  
Increased Risk ◽  
Artery Disease

Abstract Background Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients. Objective To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). Research design and methods We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up. Results Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72). Conclusions This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline level of Sortilin levels, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin serum levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, Sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between Sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using Sortilin levels the prediction of MACE incidence improved [area under the curve (AUC) = 0.94] and MALE (AUC = 0.72).Conclusions: This study demonstrates that Sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

The association of peripheral artery disease with renal function and albuminuria in diabetic patients

2014 ◽  
Author(s):  
Dong Sun Kim ◽  
Jung Hwan Park ◽  
Kyu Jeung Ahn ◽  
Bong Soo Cha
Keyword(s):  
Renal Function ◽  
Peripheral Artery Disease ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Artery Disease

High prevalence of lower extremity peripheral artery disease in type 2 diabetes patients with diabetic nephropathy and the role of netrin-1 levels

2017 ◽  
Author(s):  
Ahmet Kor ◽  
Suleyman Baldane ◽  
Suleyman Hilmi Ipekci ◽  
Kamile Marakoglu ◽  
Ali Altinok ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
High Prevalence ◽  
Artery Disease ◽  
Diabetes Patients

Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence

2019 ◽  
Vol 24 (38) ◽  
pp. 4511-4515 ◽  
Author(s):  
A. Koutsoumpelis ◽  
C. Argyriou ◽  
K.M. Tasopoulou ◽  
E.I. Georgakarakos ◽  
G.S. Georgiadis
Keyword(s):  
Peripheral Artery Disease ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Current Evidence ◽  
Peripheral Artery ◽  
Cardiac Events ◽  
Traditional Therapy ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Artery Disease

Background: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. Methods: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. Results: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. Conclusion: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.

Contemporary Role of Intravascular Lithotripsy in the Management of Peripheral Artery Disease

2021 ◽  
Vol 23 (7) ◽  
Author(s):  
Hafeez Ul Hassan Virk ◽  
Luai Tabaza ◽  
Talal Almas ◽  
Jon C. George
Keyword(s):  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Artery Disease

A Targeted Literature Review of the Disease Burden in Patients With Symptomatic Peripheral Artery Disease

Angiology ◽  
2019 ◽  
Vol 71 (4) ◽  
pp. 303-314
Author(s):  
Rupert Bauersachs ◽  
Sebastian Debus ◽  
Mark Nehler ◽  
Maria Huelsebeck ◽  
Janita Balradj ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Disease Burden ◽  
Ankle Brachial Index ◽  
Peripheral Artery ◽  
Economic Burden Of Disease ◽  
Surgical Interventions ◽  
Treatment Practice ◽  
Patient Profile ◽  
Increased Risk ◽  
Artery Disease

Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle–brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.

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