Differences between transmitter depletion in human heart hypertrophy and experimental cardiac hypertrophy in Goldblatt rats

1980 ◽  
pp. 118-125
Author(s):  
F. Borchard
Keyword(s):  
Cardiac Hypertrophy ◽  
Human Heart ◽  
Heart Hypertrophy

Cardiac Hypertrophy: A Risk Factor for QT-Prolongation and Cardiac Sudden Death

2006 ◽  
Vol 34 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Y. James Kang
Keyword(s):  
Risk Factor ◽  
Sudden Death ◽  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Qt Prolongation ◽  
Heart Hypertrophy ◽  
Compensatory Response ◽  
Genomics And Proteomics ◽  
Cardiac Sudden Death

Cardiac hypertrophy was viewed as a compensatory response to hemodynamic stress. However, cumulative evidence obtained from studies using more advanced technologies in human patients and animal models suggests that cardiac hypertrophy is a maladaptive process of the heart in response to intrinsic and extrinsic stimuli. Although hypertrophy can normalize wall tension, it is a risk factor for QT-prolongation and cardiac sudden death. Studies using molecular biology techniques such as transgenic and knockout mice have revealed many important molecules that are involved in the development of heart hypertrophy and have demonstrated signaling pathways leading to the pathogenesis. With the same approach, the consequence of heart hypertrophy has been examined. The significance of hypertrophy in the development of overt heart failure has been demonstrated and several critical molecular pathways involved in the process were revealed. A comprehensive understanding of the threats of heart hypertrophy to patients has helped to develop novel treatment strategies. The recognition of hypertrophy as a major risk factor for QT-prolongation and cardiac sudden death is an important advance in cardiac medicine. Cellular and molecular mechanisms of this risk aspect are currently under extensively exploring. These studies would lead to more comprehensive approaches to prevention of potential life threatening arrhythmia and cardiac sudden death. The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy.

Numerical hyperplasia in human heart hypertrophy

1971 ◽  
Vol 27 (12) ◽  
pp. 1435-1437 ◽  
Author(s):  
W. Sandritter ◽  
C. P. Adler
Keyword(s):  
Human Heart ◽  
Heart Hypertrophy

Gene expression in cardiac hypertrophy in rat and human heart muscle

1984 ◽  
Vol 5 (suppl F) ◽  
pp. 199-210 ◽  
Author(s):  
J. Zahringer ◽  
A. Klaubert ◽  
N. Pritzl ◽  
E. Stangl ◽  
E. Kreuzer
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Heart Muscle ◽  
Human Heart

scholarly journals Differential Regulation of ERK and mTOR Signaling Pathways in Failing Human Hearts

2020 ◽  
Author(s):  
Rebecca Autenried ◽  
Eric T. Weatherford ◽  
Yuan Zhang ◽  
Helena C. Kenny ◽  
Renata O. Pereira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Human Heart ◽  
Ventricular Remodeling ◽  
Mtor Signaling ◽  
Heart Failure Patients ◽  
Healthy Donors ◽  
End Stage

STUCTURED ABSTRACTObjectivesWe hypothesized that disruption of pathways downstream of insulin signaling characterize pathological ventricular remodeling and may provide insights into the pathophysiology of heart failure. To test this hypothesis, we examined components of the insulin signaling pathway in tissue explants from human hearts obtained from healthy donors and explants from heart failure patients with and without diabetes, receiving a heart transplant.BackgroundPathologic ventricular remodeling accompanied by hypertrophic growth is a common characteristic of heart failure including in patients with diabetes. The contribution of aberrant insulin signaling in the pathophysiology of diabetes-associated heart failure and, ventricular hypertrophy is incompletely understood.MethodsHearts of twenty non-failing donor participants and thirty-one human cardiac transplant patients were assessed for insulin signaling. Samples were sorted into four groups: non-failing non-obese (NFN), non-failing obese (NFO), failing non-diabetic (FND), and failing diabetic (FDM). Ejection fraction was assessed by echocardiography and clinically relevant systolic dysfunction was defined as left ventricular ejection fraction <50%. A clinical diabetes diagnosis was obtained from chart review. As a proxy measure of prolonged glycemia, plasma fructosamine was determined by colorimetric assay. Insulin signaling, protein phosphorylation, and total protein levels were measured by immunoblot.ResultsWhen all groups were analyzed together, hyperglycemia correlated with increased cardiac size and decreased function. Cardiac size correlated with increased levels of insulin receptor (IRb) and phosphorylated ERK but with decreased levels of phosphorylated Akt and mTOR. IRb and p-Akt correlated with fructosamine, but p-ERK and p-mTOR did not. Cardiac hypertrophy correlated with decreased GLUT1 levels, increased Hexokinase I and repression mitochondrial complexes I, III and IV in concert with activation of AMPK.ConclusionsAltered insulin signaling, characterized by increased IRb content, activation of ERK but repression of Akt and mTOR signaling pathways is present in the end-stage failing human heart. Similar divergence of insulin signaling pathways have been previously described in vascular smooth muscle.CONDENSED ABSTRACTWe hypothesized that disruption of pathways downstream of insulin signaling characterize pathological ventricular remodeling and may provide insights into pathophysiology. To test this hypothesis, we examined components of the insulin signaling pathway in tissue explants from human hearts obtained from healthy donors and explants from heart failure patients with and without diabetes, receiving a heart transplant. We found that altered insulin signaling, characterized by increased IRb content and activation of ERK but repression of Akt and mTOR signaling pathways is present in the end-stage failing human heart.HIGHLIGHTSIn this cross-sectional analysis of end-stage failing human cardiac tissue, hyperglycemia correlated with cardiac dysfunction and increased cardiac hypertrophy.While myocardial insulin resistance may exist in the PI3K-Akt-mTOR pathway in end-stage failing human hearts, ERK signaling is induced, which may contribute to cardiac hypertrophy in a manner that is independent of plasma insulin.Differential activation of branches of insulin signaling in human failing hearts, supports the concept of selective insulin resistance.These findings have implications for the consequences of modulating systemic insulin sensitivity in patients with heart failure.

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