Improvement of aortic valve stenosis by <scp>ApoA</scp>‐<scp>I</scp> mimetic therapy is associated with decreased aortic root and valve remodelling in mice

J, Trapeaux; Busseuil, David; Shi, Yonghui; Nobari, Soroush; Shustik, D; Mecteau, Mélanie; El-Hamamsy, Ismaı̈l; Lebel, Michel; Mongrain, Rosaire; Rhéaume, Éric; Tardif, Jean‐Claude

doi:10.1111/bph.12236

Cited by 25 publications

(20 citation statements)

References 44 publications

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“…Interestingly, apoA‐I was also found in explanted stenotic aortic valves 33. The latter finding could be related to the modification of apoA‐I by proteins such as matrix metalloproteinases, increasing its affinity to proteoglycans, and altering its reverse cholesterol transport function, leading to its accumulation within tissues 33, 34, 35, 36. Therefore, this lipid accumulation and retention, may act as a “warning” signal triggering the pathophysiologic processes involved in the development and progression of AS 4, 37.…”

Section: Discussionmentioning

confidence: 97%

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

Tastet

Capoulade

Shen

et al. 2018

JAHA

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BackgroundPrevious studies reported that middle‐aged patients with atherogenic lipoprotein‐lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) reflects the balance between atherogenic and anti‐atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA‐I ratio and AS hemodynamic progression and to determine whether this association varies according to age.Methods and ResultsA total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (Vpeak) measured by Doppler‐echocardiography between baseline and 2‐year follow‐up. Patients in the top tertile of apoB/apoA‐I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (Vpeak progression: 0.30 [0.09˗0.49] versus 0.16 [0.01˗0.36] m/s, P=0.02). There was a significant interaction (P=0.007) between apoB/apoA‐I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA‐I ratio had a 3.4‐fold faster AS progression compared with those in the bottom/mid tertiles (Vpeak progression: 0.34 [0.13˗0.69] versus 0.10 [−0.03˗0.31] m/s, P=0.002), whereas there was no significant difference between tertiles in the subgroup of older patients (P=0.83). After comprehensive adjustment, higher apoB/apoA‐I ratio was significantly associated with faster AS progression in the subset of younger patients (all, standardized β≥0.36; P≤0.01).ConclusionsHigher apoB/apoA‐I ratio is significantly associated with faster hemodynamic progression of AS in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of AS in younger patients, but may be are less important in older patients.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01679431.

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Section: Discussionmentioning

confidence: 97%

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

Tastet

Capoulade

Shen

et al. 2018

JAHA

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“…In this context, the beneficial effects of high-density lipoprotein cholesterol for the cardiovascular system are well established. 39,40 On a parallel note, recombinant apolipoprotein A1 Milano reversed aortic valve stenosis and positively affected valve remodeling in experimental settings. [40][41][42] In line with these data, a recent proteomic study 43 revealed that apolipoprotein A1 and fibrinogen were significantly enriched in the valves of patients submitted to aortic valve replacement as compared with normal aortic valves.…”

Section: Potential Mechanisms For the Observed Associationmentioning

confidence: 99%

“…39,40 On a parallel note, recombinant apolipoprotein A1 Milano reversed aortic valve stenosis and positively affected valve remodeling in experimental settings. [40][41][42] In line with these data, a recent proteomic study 43 revealed that apolipoprotein A1 and fibrinogen were significantly enriched in the valves of patients submitted to aortic valve replacement as compared with normal aortic valves. Although the presence of apolipoprotein A1 might be a protective mechanism against increased levels of low-density lipoprotein cholesterol, lipoprotein(a), and triglycerides on the aortic valve surface, the presence of fibrinogen seems Prevalence odds ratio (95% CI) for aortic valve sclerosis according to average alcohol consumption in the last 30 days (adjusted for age, sex, educational level, smoking, physical inactivity, and waist-to-height ratio).…”

Section: Potential Mechanisms For the Observed Associationmentioning

confidence: 99%

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis

Markus

Lieb

Stritzke

et al. 2015

ATVB

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Objective-In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the crosssectional association between average daily alcohol consumption and AVS in the general population. Approach and Results-We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted P value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19-2.14) among current abstainers and 1.56 (95% confidence interval, 1.01-2.41) among individuals with an average consumption of 60 g per day. Conclusions-Our

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“…In inflammatory conditions, PAI-1 is secreted by endothelial cells and appears to play a significant role in the progression to fibrosis (60,61). We found in other work that we can detect an increase in this cardiovascular risk factor in young Wrn Dhel/Dhel mice before they exhibit cardiac fibrosis and valvular aortic stenosis (13,37).…”

Section: Mouse Modelmentioning

confidence: 54%

“…This deletion abolishes both the helicase and exonuclease activities of the mouse Wrn protein (11). Wrn Δhel/Δhel mice develop abnormally high visceral fat content, hepatic steatosis (12), and aortic stenosis followed by cardiac fibrosis (13). In addition, Wrn Δhel/Δhel mice show an increase in genomic instability with age, an increase in the incidence of several cancer types, and a reduced mean lifespan of ;17% compared with wild-type (WT) mice (14,15).…”

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confidence: 99%

Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress response pathways in mice synthesizing a nonfunctional mutant WRN protein

et al. 2018

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Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase (WRN). Mice lacking part of the helicase domain of the WRN ortholog exhibit several phenotypic features of WS. In this study, we generated a Wrn mutant line that, like humans, relies entirely on dietary sources of vitamin C (ascorbate) to survive, by crossing them to mice that lack the gulonolactone oxidase enzyme required for ascorbate synthesis. In the presence of 0.01% ascorbate (w/v) in drinking water, double-mutant mice exhibited a severe reduction in lifespan, small size, sterility, osteopenia, and metabolic profiles different from wild-type (WT) mice. Although increasing the dose of ascorbate to 0.4% improved dramatically the phenotypes of double-mutant mice, the metabolic and cytokine profiles were different from age-matched WT mice. Finally, double-mutant mice treated with 0.01% ascorbate revealed a permanent activation of all the 3 branches of the ER stress response pathways due to a severe chronic oxidative stress in the ER compartment. In addition, markers associated with the ubiquitin-proteasome-dependent ER-associated degradation pathway were increased. Augmenting the dose of ascorbate reversed the activation of this pathway to WT levels rendering this pathway a potential therapeutic target in WS.-Aumailley, L., Dubois, M. J., Brennan, T. A., Garand, C., Paquet, E. R., Pignolo, R. J., Marette, A., Lebel, M. Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress response pathways in mice synthesizing a nonfunctional mutant WRN protein.

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Improvement of aortic valve stenosis by ApoA‐I mimetic therapy is associated with decreased aortic root and valve remodelling in mice

Abstract: BACKGROUND AND PURPOSEWe have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS.

Cited by 25 publications

References 44 publications

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis

Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress response pathways in mice synthesizing a nonfunctional mutant WRN protein

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