Cote N.,Laval University |
El Husseini D.,Laval University |
Pepin A.,Laval University |
Guauque-Olarte S.,University of Quebec |
And 14 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2012
Calcific aortic valve disease (CAVD) is a disorder related to progressive mineralization of valvular tissue that is a leading cause of heart disease. Thus far, there is no medical treatment to prevent the mineralization of aortic valves. It is generally thought that pathologic mineralization is linked to apoptosis of vascular cells. However, the role of apoptosis during mineralization as well as the survival signals for valvular interstitial cells (VICs), the main cellular component of aortic valves, remains to be identified. Here, through several lines of evidence, we show that bioavailability of extracellular ATP is a signal which determines survival or apoptosis of VICs and, in doing so, plays a major role in the development of CAVD. Specifically, in CAVD and in VIC cultures undergoing mineralization, we found a high level of the ectonucleotidase ENPP1. In addition, a genetic polymorphism in the intron 9 of the ENPP1 gene was associated with CAVD in a case-control cohort as well as with mRNA expression levels of ENPP1 in aortic valves. A high level of ENPP1 in CAVD promoted apoptosis-mediated mineralization of VICs by depleting the extracellular pool of ATP. We then documented that release of ATP by VICs promoted cell survival via the P2Y 2 receptor and the PI3K/Akt signaling pathway. Hence, our results show that level of ENPP1 modulates extracellular concentration of ATP, which is an important survival signal for VICs. These findings may help to develop novel pharmacological treatment for CAVD. © 2012 Elsevier Ltd.
Audet A.,Quebec Heart and Lung Institute Research Center |
Cote N.,Quebec Heart and Lung Institute Research Center |
Couture C.,Quebec Heart and Lung Institute Research Center |
Bosse Y.,Quebec Heart and Lung Institute Research Center |
And 4 more authors.
Histopathology | Year: 2012
Aims: Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein-derived amyloid could play a role in the development of CAVD. Methods and results: In 70 explanted CAVD valves and 15 control non-calcified aoric valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves colocalized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD. In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. Conclusions: Apo-AI is a major component of amyloid substance present wit in CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells. © 2012 Blackwell Publishing Limited.
Krishna A.,Harvard University |
Razak F.,University of Toronto |
Razak F.,Li Ka Shing Knowledge Institute |
Razak F.,Harvard University |
And 4 more authors.
American Journal of Clinical Nutrition | Year: 2015
Background: Marked increases in mean body mass index (BMI) and prevalence of obesity and overweight in the United States are well known. However, whether these average increases were accompanied by changing dispersion (or SD) remains understudied. Objective: We investigated population-level changes in the BMI distribution over time to understand how changes in dispersion reflect between-group compared with within-group inequalities in weight gain in the United States. Design: Using data from the Behavioral Risk Factor Surveillance System survey (1993-2012), we analyzed associations between mean, SD, and median BMI and BMI at the 5th and 95th percentiles for 3,050,992 non-Hispanic white, non-Hispanic black, and Hispanic men and women aged 25-64 y. Results: Overall, an increase of 1.0 in mean BMI (in kg/m2) was associated with an increase of 0.70 (95% CI: 0.67, 0.73) in the SD of BMI. A change of 1.0 in median BMI was associated with a change of 0.18 (95% CI: 0.14, 0.21) in the BMI value at the 5th percentile compared with a change of 2.94 (95% CI: 2.81, 3.07) at the 95th percentile. Quantile-quantile plots showed unequal changes in the BMI distribution, with pronounced changes at higher percentiles. Similar patterns were observed in subgroups stratified by sex, race-ethnicity, and education with non-Hispanic black women and women with less than a high school education having highest mean BMI, SD of BMI, and BMI values at the 5th and 95th percentiles. Conclusions: Mean BMI and the percentage of overweight and obese individuals do not fully describe population changes in BMI. Increases in within-group inequality in BMI represent an underrecognized characteristic of population-level weight gain. Crucially, similar increases in dispersion within groups suggest that growing inequalities in BMI at the population level are not driven by these socioeconomic and demographic factors. Future research should focus on understanding factors driving inequalities in weight gain between individuals. © 2015 American Society for Nutrition.
Le Meur J.-B.,Quebec Heart and Lung Institute Research Center |
Le Meur J.-B.,Laval University |
Lefebvre B.,Quebec National Institute Of Public Health Institute National Of Sante Publique Du Quebec |
Proulx J.-F.,Public Health Directorate |
And 5 more authors.
International Journal of Circumpolar Health | Year: 2014
Background. In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives. To describe the epidemiology of invasive pneumococcal disease (IPD) in relation to PPSV23 and PCV7 use. Study design and methods. Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997-2010. Results. A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997-2001 vs. 10/100,000 in 2004-2010 (pB0.01). Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p-0.11). Conclusion. The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.
Mathieu P.,Quebec Heart and Lung Institute Research Center |
Mathieu P.,Laval University |
Lemieux I.,Quebec Heart and Lung Institute Research Center |
Despres J.-P.,Quebec Heart and Lung Institute Research Center |
Despres J.-P.,Laval University
Clinical Pharmacology and Therapeutics | Year: 2010
Obesity, a highly prevalent condition, is heterogeneous with regard to its impact on cardiovascular disease (CVD) risk. Epidemiological observations and metabolic investigations have consistently demonstrated that the accumulation of excess visceral fat is related to an increased risk of CVD as well as several metabolic and inflammatory perturbations. In the past decade, data from several studies have served to emphasize that atherosclerosis has an inflammatory component that may contribute to several key pathophysiological processes. Study data have also highlighted the finding that the expanded visceral fat is infiltrated by macrophages that conduct cross-talk with adipose tissue through several significant mechanisms. In this review, we provide, in the context of CVD risk, an up-to-date account of the complex interactions that occur between a dysfunctional adipose tissue phenotype and inflammation. © 2010 American Society2010 American Society for Clinical Pharmacology and Therapeutics.