Dataset Information

The tricuspid valve also maladapts as shown in sheep with biventricular heart failure

ABSTRACT: Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, we induced biventricular heart failure in sheep that developed tricuspid valve leakage. In the anterior leaflets of those animals, we investigated maladaptation on multiple scales. We demonstrated alterations on the protein and cell-level, leading to tissue growth, thickening, and stiffening. These data provide a new perspective on a poorly understood, yet highly prevalent disease. Our findings may motivate novel therapy option for many currently untreated patients with leaky tricuspid valves.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Ovis Aries

TISSUE(S): Heart, Fibroblast

DISEASE(S): Tricuspid Valve Disease

SUBMITTER: Carla Lacerda

LAB HEAD: Manuel Rausch

PROVIDER: PXD022719 | Pride | 2021-09-09

REPOSITORIES: Pride

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The tricuspid valve also maladapts as shown in sheep with biventricular heart failure.

Meador William D WD Mathur Mrudang M Sugerman Gabriella P GP Malinowski Marcin M Jazwiec Tomasz T Wang Xinmei X Lacerda Carla Mr CM Timek Tomasz A TA Rausch Manuel K MK

eLife 20201215

Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve-extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, w ...[more]

PMID: 33320094

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Project description:Multiple molecular and cellular mechanisms are associated with the initiation and progression of aortic valve disease. Alterations in ECM remodeling, increased expression of pro-inflammatory cytokines, calcification, lipid deposition and changes in valve cell phenotype have demonstrated roles in development of aortic valve disease. Mechanical stimulation has a significant role in determining the physiological properties of valve tissue and an altered hemodynamic environment may result in pathological changes. We used microarrays to detail the global of gene expression profiles underlying valve remodeling during valve exposure to of two levels of cyclic mechanical pressure (normotensive 0-80mmHg and hypertensive 0-120mmHg ) on porcine valve tissue transcriptome using Sus Scrofa cDNA microarrays from Affymetrix and we identified distinct classes of up-regulated genes during this process. Hybridizations were carried out with RNA isolated from six independetn samples of valve tissue exposed to normotensive and hypertensive pressure for 24 hours at 1hz frecuency. Differentially expressed genes were identified by The t test with the option of unequal variance was used to calculate P values for each gene. The fold change and Q values for each gene were calculated with SAM program with permutation of 500 . Biological modeling of the differentially expressed genes (DE) was carried out based on GO groups and network analysis in ingenuity Pathway Analysis (IPA). Experiment Overall Design: The experimental design included three biological samples of porcine valve leaflets exposed to cyclic pressures of 0-80 or 0-120 mmHg for 24 hours, representing normotensive and hypertensive diastolic transvalvular pressure, respectively. Using Affymetrix porcine microarrays, we compared global gene expression profiles of aortic valve leaflets exposed to elevated and normal physiological pressure conditions . The effects of cyclic pressure on the transcriptome was determined by comparing the quantity and magnitud of change in gene expression levels of valve leflets, as well evaluating the molecular function each gene has in the cell,in the presence of hypertennsive (experimental) and normotensve pressurec (control).

Dataset Information

The tricuspid valve also maladapts as shown in sheep with biventricular heart failure

Publications

The tricuspid valve also maladapts as shown in sheep with biventricular heart failure.

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