Vicky E. MacRae
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View article: Enpp1 inhibition: a promising oral therapy for later-onset hypophosphatasia
Enpp1 inhibition: a promising oral therapy for later-onset hypophosphatasia Open
Hypophosphatasia (HPP) is a rare, inherited metabolic bone disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme encoded by the ALPL gene. Loss-of-function mutations in ALPL lead to reduc…
View article: Nutrient restriction protects against valve interstitial cell calcification by upregulating ubiquitin mediated proteolysis
Nutrient restriction protects against valve interstitial cell calcification by upregulating ubiquitin mediated proteolysis Open
Introduction: Calcific aortic valve disease (CAVD) is a common and progressive valvular heart disease characterised by the pathological calcification of valve interstitial cells (VICs). Current clinical treatments, such as surgical valve r…
View article: Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells
Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells Open
Autophagy is a highly conserved cellular recycling process essential for homeostasis in all eukaryotic cells. Lipid accumulation and its regulation by autophagy are key areas of research for understanding metabolic disorders in human and m…
View article: Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration
Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration Open
Myxomatous mitral valve degeneration (MMVD) is one of the most important age-dependent degenerative heart valve disorders in both humans and dogs. It is characterized by the aberrant remodeling of extracellular matrix (ECM), regulated by s…
View article: The N6-methyladenosine demethylase ALKBH5 is a novel epigenetic regulator of aortic valve calcification
The N6-methyladenosine demethylase ALKBH5 is a novel epigenetic regulator of aortic valve calcification Open
Aims Calcific aortic valve disease (CAVD) is a common heart valve disease with significant clinical consequences. The mechanisms that drive the pathogenesis of CAVD remain to be fully elucidated. N6-methyladenosine (m6A), the most prevalen…
View article: Mitochondrial Dysfunction as a Potential Mechanism Mediating Cardiac Comorbidities in Parkinson’s Disease
Mitochondrial Dysfunction as a Potential Mechanism Mediating Cardiac Comorbidities in Parkinson’s Disease Open
Individuals diagnosed with Parkinson’s disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development …
View article: Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder
Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder Open
Chronic kidney disease–mineral and bone disorder (CKD-MBD) presents with extra-skeletal calcification and renal osteodystrophy (ROD). The origins of ROD likely lie with elevated uremic toxins and/or an altered hormonal profile but the cell…
View article: TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease
TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease Open
Background TGFβ signaling appears to contribute to the pathogenesis of myxomatous mitral valve disease (MMVD) in both dogs and humans. However, little is known about the extent of the downstream signaling changes that will then affect cell…
View article: <scp>PFKFB3</scp> ‐driven vascular smooth muscle cell glycolysis promotes vascular calcification via the altered <scp>FoxO3</scp> and lactate production
<span>PFKFB3</span> ‐driven vascular smooth muscle cell glycolysis promotes vascular calcification via the altered <span>FoxO3</span> and lactate production Open
A link between increased glycolysis and vascular calcification has recently been reported, but it remains unclear how increased glycolysis contributes to vascular calcification. We therefore investigated the role of PFKFB3, a critical enzy…
View article: <scp>TGF‐β</scp>‐induced <scp>PI3K</scp>/<scp>AKT</scp>/<scp>mTOR</scp> pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease
<span>TGF‐β</span>‐induced <span>PI3K</span>/<span>AKT</span>/<span>mTOR</span> pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease Open
PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double‐immunofluorescence examined expression of PI3K and T…
View article: p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification
p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification Open
Arterial calcification is an important characteristic of cardiovascular disease. It has key parallels with skeletal mineralization; however, the underlying cellular mechanisms responsible are not fully understood. Mitochondrial dynamics re…
View article: Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery
Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery Open
The administration of intermittent parathyroid hormone (iPTH) is anabolic to the skeleton. Recent studies with cultured osteoblasts have revealed that the expression of PHOSPHO1, a bone‐specific phosphatase essential for the initiation of …
View article: Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor
Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor Open
Vascular calcification is associated with aging, type 2 diabetes, and atherosclerosis, and increases the risk of cardiovascular morbidity and mortality. It is an active, highly regulated process that resembles physiological bone formation.…
View article: Editorial: Vascular smooth muscle cell fate and vascular remodeling: Mechanisms, therapeutic targets, and drugs, volume I
Editorial: Vascular smooth muscle cell fate and vascular remodeling: Mechanisms, therapeutic targets, and drugs, volume I Open
EDITORIAL article Front. Pharmacol., 16 August 2022Sec. Cardiovascular and Smooth Muscle Pharmacology Volume 13 - 2022 | https://doi.org/10.3389/fphar.2022.989689
View article: Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy
Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy Open
Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities, a condition known as renal osteodystrophy (ROD). While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are critical for bone minera…
View article: The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration
The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration Open
Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common cause of heart failure leading to significant morbidity and mortality i…
View article: Cardiomyocytes disrupt pyrimidine biosynthesis in nonmyocytes to regulate heart repair
Cardiomyocytes disrupt pyrimidine biosynthesis in nonmyocytes to regulate heart repair Open
Various populations of cells are recruited to the heart after cardiac injury, but little is known about whether cardiomyocytes directly regulate heart repair. Using a murine model of ischemic cardiac injury, we demonstrate that cardiomyocy…
View article: Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy
Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy Open
Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities; a condition known as renal osteodystrophy (ROD). While Tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 are recognized to be critical…
View article: Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification?
Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification? Open
Mitochondria are crucial bioenergetics powerhouses and biosynthetic hubs within cells, which can generate and sequester toxic reactive oxygen species (ROS) in response to oxidative stress. Oxidative stress-stimulated ROS production results…
View article: Osteoblast‐specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase‐1 engenders insulin resistance in high‐fat diet fed mice
Osteoblast‐specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase‐1 engenders insulin resistance in high‐fat diet fed mice Open
Supraphysiological levels of the osteoblast‐enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase‐1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast‐specific Enpp1 a…
View article: PHOSPHO1 is a skeletal regulator of insulin resistance and obesity
PHOSPHO1 is a skeletal regulator of insulin resistance and obesity Open
Background The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regul…