Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression

Awwad, Lama; Goldenberg, Tomer; Langier-Goncalves, Irina; Aronheim, Ami

doi:10.3390/cells11071108

Cited by 15 publications

(19 citation statements)

References 26 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, tumor promotion phenotype was apparent with multiple mice models such as myocardial infarction (MI) [16][17][18], pressure overload (TAC) [10], and heart hypertrophy (ATF3 transgene) [11]. In addition, a chronic hypertension model with heart hypertrophy but no cardiac dysfunction resulted in enhanced tumor growth [19]. Therefore, based on the lack of tumor promotion in MDX mice, we conclude that the tumor promotion phenotype is rather dependent on the cardiac hypertrophy phenotype and independent of direct cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Tumor growth ameliorates cardiac dysfunction and dampens fibrosis in a mouse model for Duchenne Muscular Dystrophy

Achlaug

Awwad

Goncalves

et al. 2023

Preprint

View full text Add to dashboard Cite

Heart failure and cancer are known to share common risk factors. Nevertheless, until recently, these two were considered separate diseases. Nevertheless, it appears that heart failure and cancer are more connected than initially anticipated. The interplay between heart failure and cancer represents a double-edged sword. While Cardiac remodeling promotes cancer progression, tumor growth suppresses cardiac hypertrophy and reduces fibrosis deposition. Whether these two opposing interactions are connected is currently unknown. In addition, the experimental setup used was unable to distinguish whether tumor growth suppresses de novo fibrosis synthesis or is capable of dissolving existing fibrosis as well. Here we studied a clinically relevant human disease, Duchenne Muscular Dystrophy (DMD), using MDX mouse as a model for a fibrotic disease in multiple organs. Duchenne patients suffer from fibrosis of the skeletal, cardiac, and diaphragm muscles leading to cardiomyopathy, and respiratory failure with no cure. To study the mutual interaction between heart failure and cancer, we implanted murine cancer cells in MDX mice and monitored tumor growth, cardiac function, and fibrosis. Surprisingly, cardiac dysfunction failed to promote cancer progression in MDX mice. In contrast, MDX tumor-bearing mice displayed reduced fibrosis in the lungs, heart and diaphragm muscles resulting in an improvement of cardiac contractile function. The latter is at least partially mediated via macrophage polarization towards M2 in the heart and diaphragm muscles. Collectively, our data support the notion that tumor promotion due to heart failure is an independent of cardiac dysfunction amelioration by tumor growth. Additionally, these results suggest that the reduced overall fibrosis in tumor-bearing MDX mice represents suppression of de novo fibrosis deposition as well as dissolving existing fibrosis in the heart and diaphragm muscles. Harnessing tumor paradigms may provide novel therapeutic strategies for DMD patients, human fibrotic diseases, and cardiac dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor growth ameliorates cardiac dysfunction and dampens fibrosis in a mouse model for Duchenne Muscular Dystrophy

Achlaug

Awwad

Goncalves

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…While heart failure and cancer have until recently been considered separate diseases, it is becoming evident that they are highly connected and affect each other's outcome at multiple levels (3)(4)(5)(6). In particular, several recent studies using multiple mouse models for heart failure demonstrated that heart failure following myocardial infraction (7,8), and even early cardiac remodeling prior to heart failure, promote cell proliferation and cancer cell migration (9)(10)(11) and metastasis seeding (3,9,12). In addition, multiple epidemiological studies have suggested that myocardial infraction patients are at a higher risk of developing cancer with a poorer outcome (13), and the same goes for young patients with severe aortic stenosis (12,14).…”

Section: Introductionmentioning

confidence: 99%

Tumor growth ameliorates cardiac dysfunction

Awwad

Shofti

Haas

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Heart failure and cancer are the most deadly diseases worldwide. Murine models for cardiac remodeling and heart failure demonstrate that cardiac dysfunction promotes cancer progression and metastasis spread. Yet, no information is available on whether and how tumor progression affects cardiac remodeling. Here, we examined cardiac remodeling following transverse aortic constriction in the presence or absence of proliferating cancer cells. We show that tumor-bearing mice display reduced cardiac hypertrophy, lower fibrosis and improved cardiac contractile function. We further identify tumor-dependent M1-to-M2 polarization in the cardiac macrophage population as a mediator of the beneficial tumor effect on the heart. Harnessing cancer paradigms that are involved in tumor-dependent improved cardiac outcome may provide novel therapeutic strategies for cardiovascular diseases.

show abstract

“…Recent evidence suggests cardiac remodeling and cancer progression are tightly linked (Avraham et al, 2020 ). This link goes both ways: heart failure or cardiovascular disease enhances existing (Koelwyn et al, 2020 ) or new (Avraham et al, 2020 ; Awwad et al, 2022 ) tumor growth, and the onset of cancer increases incidents of atrial fibrillation and other cardiac abnormalities (Conen et al, 2016 ; Guzzetti et al, 2002 ). In this study, we show the effects of cancer on the heart, specifically HRV and cardiac structure, using pancreatic and liver cancer models.…”

Section: Introductionmentioning

confidence: 99%

Evidence of sex differences in cancer‐related cardiac complications in mouse models of pancreatic and liver cancer

Gams

Nevarez

Perkail

et al. 2023

Physiological Reports

View full text Add to dashboard Cite

Abnormal heart rate variability (HRV) is commonly observed in cancer patients who have undergone targeted therapy and/or surgery, yet the effects of cancer itself on cardiac function remain underexplored. Specifically, there is limited knowledge about sex‐specific manifestations of HRV in cancer patients. Transgenic mouse models are widely used to study different types of cancer. Here, we aimed to investigate the sex‐specific effects of cancer on cardiac function using transgenic mouse models of pancreatic and liver cancers. This study used male and female transgenic mice with cancer and wild‐type controls. Cardiac function was assessed by recording electrocardiograms in conscious mice. RR intervals were detected to determine HRV using time and frequency domain analyses. Histological analysis with Masson's trichrome staining was performed to determine structural changes. In females, increased HRV was observed in both pancreatic and liver cancer‐bearing mice. In contrast, in males, increased HRV was observed only in the liver cancer group. Male pancreatic cancer mice demonstrated autonomic balance shift showing an increase in parasympathetic to sympathetic tone. The heart rate (HR) was higher in control and liver cancer male mice groups than in females. Histological analysis did not show significant sex differences but suggested a higher degree of remodeling in liver cancer mice than in control, specifically in the right atrium and left ventricle. This study revealed sex differences in cancer's HR modulation. Specifically, female cancer mice had lower median HR and higher HRV. These findings indicate that sex must be considered when using HRV as a cancer biomarker.

show abstract

Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression

Cited by 15 publications

References 26 publications

Tumor growth ameliorates cardiac dysfunction and dampens fibrosis in a mouse model for Duchenne Muscular Dystrophy

Tumor growth ameliorates cardiac dysfunction and dampens fibrosis in a mouse model for Duchenne Muscular Dystrophy

Tumor growth ameliorates cardiac dysfunction

Evidence of sex differences in cancer‐related cardiac complications in mouse models of pancreatic and liver cancer

Contact Info

Product

Resources

About