scholarly journals Cardiomyopathy: Getting Bigger All the Time - Lessons Learned about Heart Disease from Tropomyosin

2021 ◽  
Author(s):  
David F. Wieczorek
Keyword(s):  
Heart Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Genetic Association ◽  
Basic Science ◽  
Thin Filament ◽  
Contractile Proteins ◽  
Lessons Learned ◽  
Genetic Mutations ◽  
Filament Protein ◽  
Science Investigations

In 1990, John and Christine Seidman uncovered the genetic association between mutations in sarcomeric contractile proteins and hypertrophic cardiomyopathy. Since then, the increase in knowledge and understanding of this disease has increased exponentially. Although pathologies associated with the various cardiomyopathies are vastly different, in some cases, the same proteins are causative, but with different genetic mutations. The focus of this article will be on hypertrophic and dilated cardiomyopathies, which are often caused by mutations in sarcomeric contractile proteins. Tropomyosin, a thin filament protein, serves as a paradigm to illustrate how different mutations within the same protein can generate the hypertrophic or dilated cardiomyopathic condition. As such, the significant advances in information derived from basic science investigations has led to the development of novel therapeutics in the treatment of these pathological diseases. This article will illustrate linkages which occur to bridge scientific advances to clinical treatments in cardiomyopathic patients.

Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis

2007 ◽  
Vol 293 (2) ◽  
pp. H949-H958 ◽  
Author(s):  
Ganapathy Jagatheesan ◽  
Sudarsan Rajan ◽  
Natalia Petrashevskaya ◽  
Arnold Schwartz ◽  
Greg Boivin ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Thin Filament ◽  
Calcium Sensitivity ◽  
Contractile Proteins ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Physiological Effects ◽  
Calcium Response ◽  
Normal Morphology ◽  
Filament Protein ◽  
Myofilament Calcium Sensitivity

Familial hypertrophic cardiomyopathy (FHC) is a disease caused by mutations in contractile proteins of the sarcomere. Our laboratory developed a mouse model of FHC with a mutation in the thin filament protein α-tropomyosin (TM) at amino acid 180 (Glu180Gly). The hearts of these mice exhibit dramatic systolic and diastolic dysfunction, and their myofilaments demonstrate increased calcium sensitivity. The mice also develop severe cardiac hypertrophy, with death ensuing by 6 mo. In an attempt to normalize calcium sensitivity in the cardiomyofilaments of the hypertrophic mice, we generated a chimeric α-/β-TM protein that decreases calcium sensitivity in transgenic mouse cardiac myofilaments. By mating mice from these two models together, we tested the hypothesis that an attenuation of myofilament calcium sensitivity would modulate the severe physiological and pathological consequences of the FHC mutation. These double-transgenic mice “rescue” the hypertrophic phenotype by exhibiting a normal morphology with no pathological abnormalities. Physiological analyses of these rescued mice show improved cardiac function and normal myofilament calcium sensitivity. These results demonstrate that alterations in calcium response by modification of contractile proteins can prevent the pathological and physiological effects of this disease.

scholarly journals Hypertrophic cardiomyopathy: a modern view of the problem

2020 ◽  
Vol 11 (1) ◽  
pp. 39-45
Author(s):  
Amina M. Alieva ◽  
Ilda I. Almazova ◽  
Elena V. Reznik ◽  
Tatyana V. Pinchuk ◽  
Irina E. Baykova ◽  
...  
Keyword(s):  
Heart Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Cardiac Death ◽  
Age Groups ◽  
Genetic Diagnosis ◽  
Genetic Mutations ◽  
Common Cause ◽  
Personalized Approach ◽  
Conservative And Surgical Treatment ◽  
Genetic Heart Disease

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, with a prevalence of approximately 1 in 500 among the adult cohort. It is a common etiological factor of sudden cardiac death in the young and a common cause of morbidity and mortality in all age groups. HCM is characterized by a complex pathophysiology, which is manifested by a heterogeneous clinical picture. The mechanism of development of this variant of hypertrophy is not fully understood. Currently, only a part of the genetic mutations that correlate with the development of this pathology has been identified. In this regard, the issue of genetic diagnosis of HCM is very relevant, as it will allow us to conduct advanced screening. A very important task is to develop a personalized approach in the conservative and surgical treatment of people suffering from this variant of cardiopathy.

Rheometers, Bioreactors, and Vocalization Forces: Using Basic Science Investigations to Help the Voices of Teachers

2008 ◽  
Vol 18 (3) ◽  
pp. 119-125
Author(s):  
Sarah Klemuk
Keyword(s):  
Basic Science ◽  
Tissue Growth ◽  
University Of Iowa ◽  
Support Cell ◽  
Rest Periods ◽  
Collaborative Studies ◽  
Professional Voice Users ◽  
The University ◽  
Science Investigations ◽  
Professional Voice

Abstract Collaborative studies at the University of Iowa and the National Center for Voice and Speech aim to help the voices of teachers. Investigators study how cells and tissues respond to vibration doses simulating typical vocalization patterns of teachers. A commercially manufactured instrument is uniquely modified to support cell and tissue growth, to subject tissues to vocalization-like forces, and to measure viscoelastic properties of tissues. Through this basic science approach, steps toward safety limits for vocalization and habilitating rest periods for professional voice users will be achieved.

Binding of adenylosuccinate synthetase to contractile proteins of muscle

1989 ◽  
Vol 257 (1) ◽  
pp. C29-C35 ◽  
Author(s):  
J. P. Manfredi ◽  
R. Marquetant ◽  
A. D. Magid ◽  
E. W. Holmes
Keyword(s):  
Ionic Strength ◽  
Dissociation Constant ◽  
Thin Filament ◽  
Contractile Proteins ◽  
Purine Nucleotide ◽  
Apparent Dissociation Constant ◽  
Thin Filaments ◽  
Adenylosuccinate Synthetase ◽  
Purine Nucleotide Cycle ◽  
Low Ionic Strength

The muscle isozyme of adenylosuccinate synthetase (AdSS), an enzyme of the purine nucleotide cycle, has previously been shown to bind to purified F-actin in buffers of low ionic strength and pH (Ogawa et al. Eur. J. Biochem. 85: 331-338, 1978). We have extended these observations by measuring the association of both crude and purified AdSS with the contractile proteins of muscle in buffers of physiological ionic strength and pH. Under these conditions, the enzyme binds to F-actin, actin-tropomyosin complexes, reconstructed thin filaments, and myofibrils but not to myosin. The apparent dissociation constant of 1.2 microM and binding maximum of 2.6 nmol enzyme/mg myofibrils indicate that binding of AdSS to myofibrils can be physiologically significant. The results suggest that AdSS in muscle may be associated with the thin filament of myofibrils.

Coronary heart disease of females: lessons learned from nonhuman primates

2009 ◽  
Vol 71 (9) ◽  
pp. 785-793 ◽  
Author(s):  
Thomas B. Clarkson ◽  
Margaret H. Mehaffey
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Nonhuman Primates ◽  
Lessons Learned

Value of Electrocardiogram in the Differentiation of Hypertensive Heart Disease, Hypertrophic Cardiomyopathy, Aortic Stenosis, Amyloidosis, and Fabry Disease

2012 ◽  
Vol 109 (4) ◽  
pp. 587-593 ◽  
Author(s):  
Mehdi Namdar ◽  
Jan Steffel ◽  
Sandra Jetzer ◽  
Christian Schmied ◽  
David Hürlimann ◽  
...  
Keyword(s):  
Heart Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Aortic Stenosis ◽  
Fabry Disease ◽  
Hypertensive Heart Disease
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