ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients

Gellen, Barnabas; Thorin‐Trescases, Nathalie; Sosner, P.; Gand, Elise; Saulnier, Pierre‐Jean; Ragot, Stéphanie; Fraty, M.; Laugier, S.; Ducrocq, Grégory; Montaigne, David; Llaty, P.; Rigalleau, Vincent; Zaoui, Philippe; Halimi, Jean‐Michel; Roussel, Ronan; Thorin, Éric; Hadjadj, Samy

doi:10.1007/s00125-016-4066-5

Cited by 31 publications

(32 citation statements)

References 49 publications

(56 reference statements)

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“…56 Moreover, in a prospective, monocentric cohort of European patients with type 2 diabetes but without end-stage renal disease (followed for a median of 6.0 years with death as a primary endpoint and major adverse CV events (known as MACE) such as death, myocardial infarction or stroke as a secondary endpoints), serum ANGPTL2 concentrations were independently associated with death and MACE. 60 Taken together with observations suggesting that ANGPTL2 promotes CVD development and progression in mice, 25 circulating ANGPTL2 levels could be viewed as a candidate biomarker for risk stratification relevant to CVD development and progression in both type 2 diabetic patients and…”

Section: Circulating Angptl2 Levels In Cvd and Predisposing Conditionsmentioning

confidence: 92%

ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

Oike

Tian

Miyata

et al. 2017

Circ J

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inflammation, 11,12 and emerging evidence reveals that senescent cells secrete factors that cause chronic local tissue inflammation associated with age-associated diseases. [13][14][15] This newly identified cellular senescence condition, termed the senescence-associated secretory phenotype (SASP), is now recognized as creating a common pathological environment that encourages development of age-associated diseases, including CVD. 13,15, 16 Many of our previous studies have revealed that the expression and secretion of angiopoietin-like 2 (ANGPTL2) significantly increase in cells stressed by pathophysiologic stimuli such as hypoxia, reactive oxidative species, and pressure overload. 17-21 ANGPTL2 expression also increases in cells undergoing senescence, 22 suggesting that ANGPTL2 is a SASP factor. Moreover, excess ANGPTL2 signaling is pro-inflammatory in pathologic states and contributes to the development of aging-associated diseases such as CVD. 23-25 Thus, to understand the mechanisms underlying these conditions, we focus our discussion here on the role of ANGPTL2 in CVD. What Is ANGPTL2?Around 2000, several groups independently reported secreted glycoproteins that exhibit an N-terminal coiled-coil W orldwide, the number of patients with heart disease is increasing as populations of elderly people expand. Of the heart diseases, cardiovascular disease (CVD) and heart failure (HF) are associated with adverse health outcomes that decrease a patient's wellbeing and productivity. 1,2 Prevention of these conditions is desirable to promote healthy aging and improve patients' lifestyle.The pathologic basis of CVD is atherosclerosis caused by ectopic accumulation of cholesterol in vessel walls; 3 thus advent of therapies aimed at reducing low-density lipoprotein (LDL)-cholesterol levels has succeeded in decreasing the number of CVD events. 4,5 However, these events continue to occur, even in patients whose LDLcholesterol levels have been lowered by antidyslipidemia treatment, 1,2,4,5 indicating that the pathologies underlying CVD are highly complex. In addition to dyslipidemia, other factors such as smoking, hypertension, diabetes, ventral obesity, male sex, aging, genetic factors, and family history of CVD are well-established risk factors, 6-8 and the number of patients with dyslipidemia, diabetes, and hypertension also increases with age. 9 Recently, it was shown that chronic vascular inflammation accelerates atherosclerosis development. 10 Interestingly, aging, smoking, diabetes, and dyslipidemia all induce chronic In parallel with the increase in the number of elderly people worldwide, the number of patients with heart disease is also rapidly increasing. Of the heart diseases, cardiovascular disease (CVD) and heart failure (HF) are strongly associated with adverse health outcomes that decrease productivity in later years. Recently, ANGPTL2, a secreted glycoprotein and member of the angiopoietin-like protein family, has received attention as a causal player in the development of CVD and HF. Prolonged ANGPTL2 auto...

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Section: Circulating Angptl2 Levels In Cvd and Predisposing Conditionsmentioning

confidence: 92%

ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

Oike

Tian

Miyata

et al. 2017

Circ J

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“…The latest update available (2015) was considered in the present analysis. Detailed description of study population, outcome criteria, adjudication procedure and biological procedures has been published previously [23]. Samples were stored at −80°C at the Poitiers biobanking facility (CRB 0033-00068; www.chu-poitiers.fr/specialites/centre-ressources-biologiques).…”

Section: Methodsmentioning

confidence: 99%

Prognostic value of plasma MR-proADM vs NT-proBNP for heart failure in people with type 2 diabetes: the SURDIAGENE prospective study

Fraty¹,

Gand

Fumeron

et al. 2018

Diabetologia

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“…Furthermore, increased levels of ANGPTL2 were reported in diabetes [ 5 , 44 – 47 ], chronic kidney disease [ 9 , 46 , 48 , 49 ], cardiovascular diseases [ 5 , 7 , 8 , 26 , 50 – 57 ], metabolic disorders including obesity [ 5 , 55 , 58 – 60 ], and other diseases (for review, [ 6 ]), including autoimmune diseases such as dermatomyositis [ 61 ] and rheumatoid arthritis [ 62 ] (Tables 1 and 3 ). ANGPTL2 levels in the circulation were also reported to be a predictor of major adverse cardiac events and death in diabetic [ 45 ] and renal transplant [ 48 ] patients. Despite this multitude of evidence of pathological higher circulating levels of ANGPTL2 in different diseases, it remains to determine (a) what are the sources of circulating ANGPTL2?…”

Section: Introductionmentioning

confidence: 99%

High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation

Thorin‐Trescases

Thorin

2017

Oxidative Medicine and Cellular Longevity

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Angiopoietin-like 2 (ANGPTL2) is a proinflammatory protein belonging to the angiopoietin-like family. ANGPTL2 is secreted and detected in the systemic circulation. Different observational clinical studies reported that circulating levels of ANGPTL2 increase significantly in various chronic inflammatory diseases and showed associations between ANGPTL2 levels and diagnosis and/or prognosis of cardiovascular diseases, diabetes, chronic kidney disease, and various types of cancers. However, these studies did not address the following questions: (a) what are the sources of circulating ANGPTL2? (b) How and by which mechanisms an increase in circulating ANGPTL2 contributes to the pathogenesis of chronic inflammatory diseases? (c) Does an increase in circulating levels of ANGPTL2 measured in a well-defined chronic medical condition originate from a specific cell type? Mechanistic hypotheses have been proposed based on studies performed in mice and cultured cells, and proinflammatory, prooxidative, proangiogenic, proliferative, and antiapoptotic properties of ANGPTL2 have been reported. The aim of this review is to propose answers concerning the potential sources of circulating ANGPTL2 and its common pathological properties associated with various chronic inflammatory diseases and death in humans. We believe that high circulating ANGPTL2 levels are more than an inflammatory marker and may reflect the senescent cellular load of an individual.

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ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients

Cited by 31 publications

References 49 publications

ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

Prognostic value of plasma MR-proADM vs NT-proBNP for heart failure in people with type 2 diabetes: the SURDIAGENE prospective study

High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation

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ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients

Cited by 31 publications

References 49 publications

ANGPTL2 ― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

ANGPTL2 ― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

Prognostic value of plasma MR-proADM vs NT-proBNP for heart failure in people with type 2 diabetes: the SURDIAGENE prospective study

High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation

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ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―

ANGPTL2　― A New Causal Player in Accelerating Heart Disease Development in the Aging ―