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Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis.
Swiger KJ, Friedman EA, Brittain EL, Tomasek KA, Huang S, Su YR, Sawyer DB, Lenihan DJ
(2016) Amyloid 23: 242-248
MeSH Terms: Aged, Amyloidosis, Biomarkers, Cardiomyopathies, Cohort Studies, Diagnosis, Differential, Female, Galectin 3, Heart Failure, Systolic, Hepatocyte Growth Factor, Humans, Hypertrophy, Left Ventricular, Immunoglobulin Light Chains, Interleukin-6, Male, Middle Aged, Prealbumin, Registries, Survival Analysis, Vascular Endothelial Growth Factor A
Show Abstract · Added June 7, 2018
BACKGROUND - Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.
METHODS - Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.
RESULTS - HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively).
CONCLUSIONS - HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.
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Association of Fitness in Young Adulthood With Survival and Cardiovascular Risk: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.
Shah RV, Murthy VL, Colangelo LA, Reis J, Venkatesh BA, Sharma R, Abbasi SA, Goff DC, Carr JJ, Rana JS, Terry JG, Bouchard C, Sarzynski MA, Eisman A, Neilan T, Das S, Jerosch-Herold M, Lewis CE, Carnethon M, Lewis GD, Lima JA
(2016) JAMA Intern Med 176: 87-95
MeSH Terms: Adolescent, Adult, Asymptomatic Diseases, Cardiovascular Diseases, Coronary Artery Disease, Exercise Test, Female, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Longitudinal Studies, Male, Middle Aged, Mortality, Obesity, Physical Fitness, Proportional Hazards Models, Prospective Studies, Tomography, X-Ray Computed, Ultrasonography, United States, Vascular Calcification, Young Adult
Show Abstract · Added September 29, 2016
IMPORTANCE - Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear.
OBJECTIVE - To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD).
DESIGN, SETTING, AND PARTICIPANTS - Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up.
MAIN OUTCOMES AND MEASURES - The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated.
RESULTS - Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found.
CONCLUSIONS AND RELEVANCE - Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
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23 MeSH Terms
FGFR1 signaling in hypertrophic chondrocytes is attenuated by the Ras-GAP neurofibromin during endochondral bone formation.
Karolak MR, Yang X, Elefteriou F
(2015) Hum Mol Genet 24: 2552-64
MeSH Terms: Animals, Chondrocytes, Chondrogenesis, Collagen Type II, Female, Gene Expression, Gene Knockout Techniques, Growth Plate, Hypertrophy, Male, Mice, Mice, Knockout, Neurofibromin 1, Osteoclasts, Osteogenesis, Phenotype, Phenylurea Compounds, Protein Transport, Pyrimidines, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 3, Signal Transduction
Show Abstract · Added February 19, 2015
Aberrant fibroblast growth factor receptor 3 (FGFR3) signaling disrupts chondrocyte proliferation and growth plate size and architecture, leading to various chondrodysplasias or bone overgrowth. These observations suggest that the duration, intensity and cellular context of FGFR signaling during growth plate chondrocyte maturation require tight, regulated control for proper bone elongation. However, the machinery fine-tuning FGFR signaling in chondrocytes is incompletely defined. We report here that neurofibromin, a Ras-GAP encoded by Nf1, has an overlapping expression pattern with FGFR1 and FGFR3 in prehypertrophic chondrocytes, and with FGFR1 in hypertrophic chondrocytes during endochondral ossification. Based on previous evidence that neurofibromin inhibits Ras-ERK signaling in chondrocytes and phenotypic analogies between mice with constitutive FGFR1 activation and Nf1 deficiency in Col2a1-positive chondrocytes, we asked whether neurofibromin is required to control FGFR1-Ras-ERK signaling in maturing chondrocytes in vivo. Genetic Nf1 ablation in Fgfr1-deficient chondrocytes reactivated Ras-ERK1/2 signaling in hypertrophic chondrocytes and reversed the expansion of the hypertrophic zone observed in mice lacking Fgfr1 in Col2a1-positive chondrocytes. Histomorphometric and gene expression analyses suggested that neurofibromin, by inhibiting Rankl expression, attenuates pro-osteoclastogenic FGFR1 signaling in hypertrophic chondrocytes. We also provide evidence suggesting that neurofibromin in prehypertrophic chondrocytes, downstream of FGFRs and via an indirect mechanism, is required for normal extension and organization of proliferative columns. Collectively, this study indicates that FGFR signaling provides an important input into the Ras-Raf-MEK-ERK1/2 signaling axis in chondrocytes, and that this input is differentially regulated during chondrocyte maturation by a complex intracellular machinery, of which neurofibromin is a critical component.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Serum parathyroid hormone and 25-hydroxyvitamin D concentrations and risk of incident heart failure: the Multi-Ethnic Study of Atherosclerosis.
Bansal N, Zelnick L, Robinson-Cohen C, Hoofnagle AN, Ix JH, Lima JA, Shoben AB, Peralta CA, Siscovick DS, Kestenbaum B, de Boer IH
(2014) J Am Heart Assoc 3: e001278
MeSH Terms: Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Comorbidity, Cross-Sectional Studies, Female, Heart Failure, Humans, Hypertrophy, Left Ventricular, Incidence, Kaplan-Meier Estimate, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Parathyroid Hormone, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation, Vitamin D
Show Abstract · Added September 19, 2017
BACKGROUND - Heart failure (HF) is common and is associated with high mortality. We aimed to determine associations of serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25[OH]D) with incident HF and left ventricular mass.
METHODS AND RESULTS - Among 6459 participants in the community-based Multi-Ethnic Study of Atherosclerosis, all of whom were free of prevalent clinical cardiovascular disease, we measured serum concentrations of PTH and 25(OH)D at the baseline examination. In longitudinal analyses, we tested associations of PTH and 25(OH)D with incident HF events, adjudicated by a panel of physicians. In cross-sectional analyses of a subset of 4763 participants, we tested associations of PTH and 25(OH)D with left ventricular mass, measured by cardiac magnetic resonance imaging at baseline. Multivariable Cox proportional hazard and linear regression models were adjusted for demographics, physical examination measures, comorbidity, kidney function, and other mineral metabolism markers. Mean age was 62 years and 53% of participants were female. There were 180 incident HF events over a median (interquartile range) follow-up time of 8.46 (7.67 to 8.63) years. Compared with participants with PTH <65 pg/mL, PTH ≥65 pg/mL was associated with a 50% greater risk of incident HF (95% CI: 3% to 210%) and a 5.3 g higher left ventricular mass (95% CI: 2.6, 7.9 g). In contrast, there was no association of 25(OH)D with risk of incident HF or elevated left ventricular mass.
CONCLUSIONS - In a racially/ethnically diverse population without prevalent cardiovascular disease, higher serum PTH concentration was associated with increased left ventricular mass and increased risk of incident HF. Further studies should be pursued to determine whether PTH excess may be a modifiable risk factor for HF.
© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
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28 MeSH Terms
Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension.
Nozik-Grayck E, Woods C, Taylor JM, Benninger RK, Johnson RD, Villegas LR, Stenmark KR, Harrison DG, Majka SM, Irwin D, Farrow KN
(2014) Am J Physiol Lung Cell Mol Physiol 307: L868-76
MeSH Terms: Animals, Blood Pressure, Cyclic GMP, Cyclic Nucleotide Phosphodiesterases, Type 5, Estrogen Antagonists, GTP Cyclohydrolase, Guanylate Cyclase, Hypertension, Pulmonary, Hypertrophy, Right Ventricular, Hypoxia, Lung, Mice, Mice, Knockout, Nitric Oxide Synthase Type III, Pulmonary Artery, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Soluble Guanylyl Cyclase, Superoxide Dismutase, Tamoxifen
Show Abstract · Added March 31, 2015
Excess superoxide has been implicated in pulmonary hypertension (PH). We previously found lung overexpression of the antioxidant extracellular superoxide dismutase (EC-SOD) attenuates PH and pulmonary artery (PA) remodeling. Although comprising a small fraction of total SOD activity in most tissues, EC-SOD is abundant in arteries. We hypothesize that the selective loss of vascular EC-SOD promotes hypoxia-induced PH through redox-sensitive signaling pathways. EC-SOD(loxp/loxp) × Tg(cre/SMMHC) mice (SMC EC-SOD KO) received tamoxifen to conditionally deplete smooth muscle cell (SMC)-derived EC-SOD. Mice were exposed to hypobaric hypoxia for 35 days, and PH was assessed by right ventricular systolic pressure measurements and right ventricle hypertrophy. Vascular remodeling was evaluated by morphometric analysis and two-photon microscopy for collagen. We examined cGMP content and soluble guanylate cyclase expression and activity in lung, lung phosphodiesterase 5 (PDE5) expression and activity, and expression of endothelial nitric oxide synthase and GTP cyclohydrolase-1 (GTPCH-1), the rate-limiting enzyme in tetrahydrobiopterin synthesis. Knockout of SMC EC-SOD selectively decreased PA EC-SOD without altering total lung EC-SOD. PH and vascular remodeling induced by chronic hypoxia was augmented in SMC EC-SOD KO. Depletion of SMC EC-SOD did not impact content or activity of lung soluble guanylate cyclase or PDE5, yet it blunted the hypoxia-induced increase in cGMP. Although total eNOS was not altered, active eNOS and GTPCH-1 decreased with hypoxia only in SMC EC-SOD KO. We conclude that the localized loss of PA EC-SOD augments chronic hypoxic PH. In addition to oxidative inactivation of NO, deletion of EC-SOD seems to reduce eNOS activity, further compromising pulmonary vascular function.
Copyright © 2014 the American Physiological Society.
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20 MeSH Terms
Coronary artery dilation and left ventricular hypertrophy do not predict morbidity in children with sickle cell disease.
Johnson MC, Johnikin MJ, Euteneuer JC, DeBaun MR, Hildebolt C
(2015) Pediatr Blood Cancer 62: 115-9
MeSH Terms: Adolescent, Anemia, Sickle Cell, Case-Control Studies, Child, Coronary Artery Disease, Echocardiography, Female, Follow-Up Studies, Humans, Hypertrophy, Left Ventricular, Male, Morbidity, Prevalence, Prognosis, Retrospective Studies, United States, Young Adult
Show Abstract · Added October 7, 2014
BACKGROUND - Little is known about the clinical significance of coronary artery dilation (CAD) and left ventricular hypertrophy (LVH) in patients with sickle cell disease (SCD).
PROCEDURE - In a retrospective cohort, we studied the prevalence of CAD and LVH in 101 children with SCD in comparison to 93 healthy African-American patients without SCD. Hospital days, number of admissions, and intensive care unit admission after the echocardiogram were assessed as measures of morbidity.
RESULTS - Multivariable analysis of echocardiographic measures of LVH and CAD did not predict subsequent intensive care unit admission, hospital days/year or number of hospital admissions/year during a median follow-up time of 6.1 years. LVH as measured by left ventricular mass index was present in 46% of children with SCD and was inversely related to age (P = 0.0004). Height-indexed dimensions in children with SCD demonstrated that the prevalence of dilation was 49% for the left main coronary artery (LMCA), 29% for the left anterior descending (LAD), and 6% for the right coronary artery (RCA). LMCA dilation was related to relative wall thickness (P = 0.006), inversely to age (P < 0.0006) and weakly to disease severity as determined by hemoglobin (P = 0.03). CAD and LVH were not related to a clinical history of vaso-occlusive pain episode, acute chest syndrome, or cerebrovascular accident.
CONCLUSION - LVH and CAD are common findings in children with SCD; however, they are not associated with need for subsequent hospital or intensive care unit admission.
© 2014 Wiley Periodicals, Inc.
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17 MeSH Terms
Remnant growth rate after portal vein embolization is a good early predictor of post-hepatectomy liver failure.
Leung U, Simpson AL, Araujo RL, Gönen M, McAuliffe C, Miga MI, Parada EP, Allen PJ, D'Angelica MI, Kingham TP, DeMatteo RP, Fong Y, Jarnagin WR
(2014) J Am Coll Surg 219: 620-30
MeSH Terms: Aged, Embolization, Therapeutic, Female, Follow-Up Studies, Hepatectomy, Humans, Hypertrophy, Liver, Liver Failure, Liver Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Portal Vein, Postoperative Complications, Prognosis, ROC Curve, Retrospective Studies, Time Factors, Tomography, X-Ray Computed, Treatment Outcome
Show Abstract · Added February 12, 2015
BACKGROUND - After portal vein embolization (PVE), the future liver remnant (FLR) hypertrophies for several weeks. An early marker that predicts a low risk of post-hepatectomy liver failure can reduce the delay to surgery.
STUDY DESIGN - Liver volumes of 153 patients who underwent a major hepatectomy (>3 segments) after PVE for primary or secondary liver malignancy between September 1999 and November 2012 were retrospectively evaluated with computerized volumetry. Pre- and post-PVE FLR volume and functional liver volume were measured. Degree of hypertrophy (DH = post-FLR/post-functional liver volume - pre-FLR/pre-functional liver volume) and growth rate (GR = DH/weeks since PVE) were calculated. Postoperative complications and liver failure were correlated with DH, measured GR, and estimated GR derived from a formula based on body surface area.
RESULTS - Eligible patients underwent 93 right hepatectomies, 51 extended right hepatectomies, 4 left hepatectomies, and 5 extended left hepatectomies. Major complications occurred in 44 patients (28.7%) and liver failure in 6 patients (3.9%). Nonparametric regression showed that post-embolization FLR percent correlated poorly with liver failure. Receiver operating characteristic curves showed that DH and GR were good predictors of liver failure (area under the curve [AUC] = 0.80; p = 0.011 and AUC = 0.79; p = 0.015) and modest predictors of major complications (AUC = 0.66; p = 0.002 and AUC = 0.61; p = 0.032). No patient with GR >2.66% per week had liver failure develop. The predictive value of measured GR was superior to estimated GR for liver failure (AUC = 0.79 vs 0.58; p = 0.046).
CONCLUSIONS - Both DH and GR after PVE are strong predictors of post-hepatectomy liver failure. Growth rate might be a better guide for the optimum timing of liver resection than static volumetric measurements. Measured volumetrics correlated with outcomes better than estimated volumetrics.
Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
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21 MeSH Terms
Pediatric posterior reversible encephalopathy syndrome presenting with isolated cerebellar edema and obstructive hydrocephalus.
Ettinger N, Pearson M, Lamb FS, Wellons JC
(2014) J Neurosurg Pediatr 14: 344-7
MeSH Terms: Adolescent, Antihypertensive Agents, Brain Edema, Cerebellum, Drainage, Fourth Ventricle, Humans, Hydrocephalus, Hypertension, Hypertrophy, Left Ventricular, Magnetic Resonance Imaging, Male, Posterior Leukoencephalopathy Syndrome, Tomography, X-Ray Computed
Show Abstract · Added February 22, 2016
In this report, the authors describe the case of a teenage boy who presented with hypertensive emergency, posterior reversible encephalopathy syndrome, and hydrocephalus due to fourth ventricle outlet obstruction. Posterior reversible encephalopathy syndrome is a well-characterized but uncommon syndrome in children that is generally triggered by severe hypertension. The unusual clinical picture of this patient, who had isolated cerebellar edema leading to obstructive hydrocephalus, has been rarely described in children.
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14 MeSH Terms
Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis.
Powell AE, Vlacich G, Zhao ZY, McKinley ET, Washington MK, Manning HC, Coffey RJ
(2014) Am J Physiol Gastrointest Liver Physiol 307: G16-23
MeSH Terms: Adenomatous Polyposis Coli, Animals, Cell Transformation, Neoplastic, Colon, Colonoscopy, Disease Models, Animal, Genes, APC, Hypertrophy, Membrane Glycoproteins, Mice, Mice, Transgenic, Neoplastic Stem Cells, Nerve Tissue Proteins, Positron-Emission Tomography, Precancerous Conditions, Retinal Pigment Epithelium, Time Factors
Show Abstract · Added May 20, 2014
Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation in adenomatous polyposis coli (APC). The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extracolonic features, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium, may occur. The objective of this study was to develop a mouse model that simulates these features of FAP. We combined our Lrig1-CreERT2/+ mice with Apcfl/+ mice, eliminated one copy of Apc in leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1(+)) progenitor cells with tamoxifen injection, and monitored tumor formation in the colon by colonoscopy and PET. Initial loss of one Apc allele in Lrig1(+) cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extracolonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform on which therapeutic interventions can be monitored over time by colonoscopy and noninvasive imaging.
Copyright © 2014 the American Physiological Society.
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17 MeSH Terms
Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension.
Hemnes AR, Brittain EL, Trammell AW, Fessel JP, Austin ED, Penner N, Maynard KB, Gleaves L, Talati M, Absi T, Disalvo T, West J
(2014) Am J Respir Crit Care Med 189: 325-34
MeSH Terms: Animals, Biomarkers, Bone Morphogenetic Protein Receptors, Type II, Case-Control Studies, Ceramides, Familial Primary Pulmonary Hypertension, Genetic Markers, Humans, Hypertension, Pulmonary, Hypertrophy, Right Ventricular, Lipolysis, Mice, Mice, Transgenic, Mutation, Oligonucleotide Array Sequence Analysis, Oxidation-Reduction, Triglycerides
Show Abstract · Added February 28, 2014
RATIONALE - Shorter survival in heritable pulmonary arterial hypertension (HPAH), often due to BMPR2 mutation, has been described in association with impaired right ventricle (RV) compensation. HPAH animal models are insulin resistant, and cells with BMPR2 mutation have impaired fatty acid oxidation, but whether these findings affect the RV in HPAH is unknown.
OBJECTIVES - To test the hypothesis that BMPR2 mutation impairs RV hypertrophic responses in association with lipid deposition.
METHODS - RV hypertrophy was assessed in two models of mutant Bmpr2 expression, smooth muscle-specific (Sm22(R899X)) and universal expression (Rosa26(R899X)). Littermate control mice underwent the same stress using pulmonary artery banding (Low-PAB). Lipid content was assessed in rodent and human HPAH RVs and in Rosa26(R899X) mice after metformin administration. RV microarrays were performed using human HPAH and control subjects.
RESULTS - RV/(left ventricle + septum) did not rise directly in proportion to RV systolic pressure in Rosa26(R899X) but did in Sm22(R899X) (P < 0.05). Rosa26(R899X) RVs demonstrated intracardiomyocyte triglyceride deposition not present in Low-PAB (P < 0.05). RV lipid deposition was identified in human HPAH RVs but not in controls. Microarray analysis demonstrated defects in fatty acid oxidation in human HPAH RVs. Metformin in Rosa26(R899X) mice resulted in reduced RV lipid deposition.
CONCLUSIONS - These data demonstrate that Bmpr2 mutation affects RV stress responses in a transgenic rodent model. Impaired RV hypertrophy and triglyceride and ceramide deposition are present as a function of RV mutant Bmpr2 in mice; fatty acid oxidation impairment in human HPAH RVs may underlie this finding. Further study of how BMPR2 mediates RV lipotoxicity is warranted.
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17 MeSH Terms