Truncating Titin ( TTN) Variants in Chemotherapy-Induced Cardiomyopathy

Linschoten, Marijke; Teske, Arco J.; Baas, Annette F.; Vink, Aryan; Dooijes, Dennis; Baars, Hubert F.; Asselbergs, Folkert W.

doi:10.1016/j.cardfail.2017.03.003

Cited by 64 publications

(48 citation statements)

References 13 publications

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“…It should be noted that the case of dilated cardiomyopathy which develops after a myocardial infarction or ischemia is often classified as a separate disease entity: ischemic cardiomyopathy (ICM) [25,28,29,30,31]. The environmental cases can also have genetic predisposition [32,33]. If known cause is not identified, DCM is called idiopathic DCM.…”

Section: Introductionmentioning

confidence: 99%

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

Vikhorev

Vikhoreva

2018

IJMS

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About half of hypertrophic and dilated cardiomyopathies cases have been recognized as genetic diseases with mutations in sarcomeric proteins. The sarcomeric proteins are involved in cardiomyocyte contractility and its regulation, and play a structural role. Mutations in non-sarcomeric proteins may induce changes in cell signaling pathways that modify contractile response of heart muscle. These facts strongly suggest that contractile dysfunction plays a central role in initiation and progression of cardiomyopathies. In fact, abnormalities in contractile mechanics of myofibrils have been discovered. However, it has not been revealed how these mutations increase risk for cardiomyopathy and cause the disease. Much research has been done and still much is being done to understand how the mechanism works. Here, we review the facts of cardiac myofilament contractility in patients with cardiomyopathy and heart failure.

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Section: Introductionmentioning

confidence: 99%

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

Vikhorev

Vikhoreva

2018

IJMS

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“…However, patient data from breast cancer patients shows that cancer drugs can cause frameshift mutation in titin, reducing cardiac compliance and ultimately leading to cardiomyopathy. [ 186 ] More studies are needed to understand the cardiotoxic effects of chemotherapeutic and other cardiotoxic agents on CM stiffness to understand the mechanisms by which these compounds induce these changes.…”

Section: Measuring Changes To CM Stiffness In Response To Cardiotoxicmentioning

confidence: 99%

“…However, reports from studies in rabbits and humans have demonstrated altered expression of integrins and titin genes, respectively, in response to cancer drug treatment. [ 186,192 ] In both cases, rabbits and humans developed heart failure. While it is unclear if the changes in the gene expression of integrins and titin resulted in altered protein function leading to any causal effects, it is widely known that changes in the function of integrins and/or titin can impact contractility and the transmission of mechanical signals.…”

Section: Mechanotransduction and Cardiotoxicitymentioning

confidence: 99%

Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity

Blair

Pruitt

2020

Adv Healthcare Materials

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Cardiomyocytes are the motor units that drive the contraction and relaxation of the heart. Traditionally, testing of drugs for cardiotoxic effects has relied on primary cardiomyocytes from animal models and focused on short‐term, electrophysiological, and arrhythmogenic effects. However, primary cardiomyocytes present challenges arising from their limited viability in culture, and tissue from animal models suffers from a mismatch in their physiology to that of human heart muscle. Human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) can address these challenges. They also offer the potential to study not only electrophysiological effects but also changes in cardiomyocyte contractile and mechanical function in response to cardiotoxic drugs. With growing recognition of the long‐term cardiotoxic effects of some drugs on subcellular structure and function, there is increasing interest in using hiPSC‐CMs for in vitro cardiotoxicity studies. This review provides a brief overview of techniques that can be used to quantify changes in the active force that cardiomyocytes generate and variations in their inherent stiffness in response to cardiotoxic drugs. It concludes by discussing the application of these tools in understanding how cardiotoxic drugs directly impact the mechanobiology of cardiomyocytes and how cardiomyocytes sense and respond to mechanical load at the cellular level.

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“…Late cardiotoxicity was mainly related to high cumulative dosage, however, genetic factors play an important role in the occurrence of cardiotoxicity in patients with low-to moderate-dose of chemotherapy drugs, especially in patients with relatively low cumulative dose of adjuvant therapy [3][4][5][6]. Single nucleotide polymorphisms (SNPs) are the research focus for the genetic susceptibility to cardiotoxicity [7].…”

Section: Introductionmentioning

confidence: 99%

The incidence of adjuvant chemotherapy-related early-onset cardiac events in breast cancer patients and its relationship with genetic susceptibility: A prospective cohort study

Liu

Guan

Wang

et al. 2020

Preprint

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Background: Although cardiotoxicity has been widely concerned, the study of early-onset cardiotoxicity is insufficient and it is difficult to explain the occurrence of cardiotoxicity only by clinical factors in patients with low cumulative dose of chemotherapy. The purpose of this study was to investigate adjuvant chemotherapy -related cardiac events in breast cancer patients, and to find out the genetic risk factors related to early-onset cardiotoxicity . Methods: A total of 388 recruited patients completed routine blood, liver and kidney function, D-dimer, TnT, NT-proBNP (or BNP), ECG and UCG tests before and after adjuvant chemotherapy. Twenty-five single nucleotide polymorphisms were tested. Univariable and multivariable analyses were performed to identify independent risk factors. Results: A total of 256 adjuvant chemotherapy-related cardiac events were recorded in 180 patients (46.4%), and these included an abnormal ECG (37.4%), an abnormal UCG (8.8%), an elevated BNP (5.7%), and elevated TnT (0.3%). The ATG13 (rs10838611) GG genotype was a protective factor of early-onset cardiotoxicity (10% reduction in the LVEF) ([OR]= 0.188; 95% CI: 0.067-0.525; P=0.001). Conclusion: Adjuvant chemotherapy-related cardiac events are quite common in the real world. Genetic factors were closely related to the susceptibility of early-onset cardiotoxicity.

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Truncating Titin ( TTN) Variants in Chemotherapy-Induced Cardiomyopathy

Cited by 64 publications

References 13 publications

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle

Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity

The incidence of adjuvant chemotherapy-related early-onset cardiac events in breast cancer patients and its relationship with genetic susceptibility: A prospective cohort study

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