Increased Dietary Intake of Vitamin A Promotes Aortic Valve Calcification In Vivo

Huk, Danielle J.; Hammond, Harriet L.; Kegechika, Hiroyuki; Lincoln, Joy

doi:10.1161/atvbaha.112.300388

Cited by 31 publications

(25 citation statements)

References 71 publications

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“…RNA was extracted from murine VECs and pAVECs with Trizol according the manufactures protocol (Invitrogen) and cDNA and PCR reactions were performed as previously reported by our lab(31). Quantitative real-time PCR using a Step One Plus Real Time PCR system (Applied Biosystems) was used to detect changes in gene expression for Col4a2 , Itga1 , Rbm47 , Chrdl1 , Trim55 , and Hrh2 using Primetime assays from Integrated DNA Technologies; normalized to GAPDH and for α-SMA , Snai1, von Willebrand Factor (vWF) , and Tie2 using Taqman probes; normalized to 18S.…”

Section: Methodsmentioning

confidence: 99%

Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation

Anstine

Bobba

Ghadiali

et al. 2016

Journal of Molecular and Cellular Cardiology

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Risk factors of heart valve disease are well defined and prolonged exposure throughout life leads to degeneration and dysfunction in up to 33% of the population. While aortic valve replacement remains the most common need for cardiovascular surgery particularly in those aged over 65, the underlying mechanisms of progressive deterioration are unknown. In other cardiovascular systems, a decline in endothelial cell integrity and function play a major role in promoting pathological changes, and while similar mechanisms have been speculated in the valves, studies to support this are lacking. The goal of this study was to examine age-related changes in valve endothelial cell (VEC) distribution, morphology, function and transcriptomes during critical stages of valve development (embryonic), growth (post natal (PN)), maintenance (young adult) and aging (aging adult). Using a combination of in vivo mouse, and in vitro porcine assays we show that VEC function including, nitric oxide bioavailability, metabolism, endothelial-to-mesenchymal potential, membrane self repair and proliferation decline with age. In addition, density of VEC distribution along the endothelium decreases and this is associated with changes in morphology, decreased cell-cell interactions, and increased permeability. These changes are supported by RNA-seq analysis showing that focal adhesion-, cell cycle-, and oxidative phosphorylation-associated biological processes are negatively impacted by aging. Furthermore, by performing high-throughput analysis we are able to report the differential and common transcriptomes of VECs at each time point that can provide insights into the mechanisms underlying age-related dysfunction. These studies suggest that maturation of heart valves over time is a multifactorial process and this study has identified several key parameters that may contribute to impairment of the valve to maintain critical structure-function relationships; leading to degeneration and disease.

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Section: Methodsmentioning

confidence: 99%

Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation

Anstine

Bobba

Ghadiali

et al. 2016

Journal of Molecular and Cellular Cardiology

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“…Mitral and tricuspid valves were dissected from hearts of Scx +/− , and Scx +/+ ( wild type) mice at postnatal day 1 and cultured as explants on pore filters as previously described [21]. At the time of culture, BSA or 200 pM Tgfβ2 was added to the growth media [22] and explants were cultured for a further 48 hours.…”

Section: Methodsmentioning

confidence: 99%

Tgfβ-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves

Barnette¹,

Hulin²,

Ahmed³

et al. 2013

Journal of Molecular and Cellular Cardiology

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Mature heart valves are complex structures consisting of three highly organized extracellular matrix layers primarily composed of collagens, proteoglycans and elastin. Collectively, these diverse matrix components provide all the necessary biomechanical properties for valve function throughout life. In contrast to healthy valves, myxomatous valve disease is the most common cause of mitral valve prolapse in the human population and is characterized by an abnormal abundance of proteoglycans within the valve tri-laminar structure. Despite the clinical significance, the etiology of this phenotype is not known. Scleraxis (Scx) is a basic-helix-loop-helix transcription factor that we previously showed to be required for establishing heart valve structure during remodeling stages of valvulogenesis. In this study, we report that remodeling heart valves from Scx null mice express decreased levels of proteoglycans, particularly chondroitin sulfate proteoglycans (CSPGs), while overexpression in embryonic avian valve precursor cells and adult porcine valve interstitial cells increases CSPGs. Using these systems we further identify that Scx is positively regulated by canonical Tgfβ2 signaling during this process and this is attenuated by MAPK activity. Finally, we show that Scx is increased in myxomatous valves from human patients and mouse models, and overexpression in human mitral valve interstitial cells modestly increases proteoglycan expression consistent with myxomatous mitral valve phenotypes. Together, these studies identify an important role for Scx in regulating proteoglycans in embryonic and mature valve cells and suggest that imbalanced regulation could influence myxomatous pathogenesis.

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“…However, it is still unclear whether dietary factors are significant independent risk factors for developing CAC. It is plausible that dietary factors increase risk of developing CAC since previous findings have shown that CAC is related to intake of phosphorous, vitamin A and vitamin D [9,10,11]. Nevertheless, there is little information supporting the relationships between CAC and macronutrients, such as carbohydrate, protein and fat intake.…”

Section: Introductionmentioning

confidence: 99%

Composition of Dietary Macronutrient Intake Is Not Associated with Prevalence of Coronary Artery Calcification in Healthy Korean Adults

Sung

Byrne

et al. 2014

Ann Nutr Metab

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Background and Aims: There is little information supporting the relationships between macronutrients and pre-clinical atherosclerosis. The aim of this study was to identify whether dietary macronutrient content is related with CAC. Methods: 10,793 healthy Korean adults in a cohort were enrolled. Subjects were divided into CAC (CAC score >0) or non-CAC group (CAC score = 0). Intake of energy, carbohydrate (CHO), protein and fat were obtained using food frequency questionnaire (FFQ). Macronutrient composition was expressed as the ratio of energy from each macronutrient to total energy. Subjects were classified into three groups according to tertiles of intake for each macronutrient. To investigate the association between macronutrient intake and CAC, multiple regression analysis was conducted according to tertile groups of each macronutrient. Results: The prevalence of CAC significantly differed among tertile groups of CHO and fat intake in men (p < 0.001, p < 0.01) and women (p < 0.05, p < 0.01). However, multiple logistic regression analysis revealed that the odds ratios (ORs) for CAC were not significantly different among tertile groups of each macronutrient intake after adjustment in men (CHO: OR = 0.965 [95% CI = 0.826-1.129]; protein: OR = 1.029 [95% CI = 0.881-1.201]; fat: OR = 1.015 [95% CI = 0.868-1.188]) and women (CHO: OR = 1.158 [95% CI = 0.550-2.438]; protein: OR = 1.261 [95% CI = 0.629-2.528]; fat: OR = 0.625 [95% CI = 0.286-1.365]). Conclusions: The prevalence of CAC may not be associated with composition of dietary macronutrient intake in in healthy Korean adults. © 2014 S. Karger AG, Basel

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Increased Dietary Intake of Vitamin A Promotes Aortic Valve Calcification In Vivo

Cited by 31 publications

References 71 publications

Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation

Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation

Tgfβ-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves

Composition of Dietary Macronutrient Intake Is Not Associated with Prevalence of Coronary Artery Calcification in Healthy Korean Adults

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