TABLE 1.
Preclinical models that describe metabolic alterations in heart disease, cancer, and link both diseases (interdisciplinary studies).
| Factor | Metabolic disorder | Intervention | Cardiovascular studies | Cancer studies | Interdisciplinary studies |
| Inflammation | |||||
| IFN-γ | Cachexia | Anti-IFN-γ antibodies | Matthys et al., 1991a | ||
| IL-6 | Cachexia | IL-6 KO animals | Cahlin et al., 2000 | ||
| Cachexia | Anti-IL-6 antibodies | Strassmann et al., 1992 | |||
| Muscular atrophy | IL-6 transgenic mice | Tsujinaka et al., 1995 | |||
| Muscular atrophy | IL-6 injections | Haddad et al., 2005 | |||
| TNF-α | Cachexia | Injection of TNF-α -producing CHO cells | Oliff et al., 1987 | ||
| Cachexia | Pharmacological inhibition of TNF-α | Steffen et al., 2008 | |||
| IL-1β | Cachexia | Injection of IL1-receptor antagonists | Strassmann et al., 1993 | ||
| TGF-β signaling | Cachexia and loss of heart mass | Blockage of Activin ActRIIB pathway in C26 tumor-bearing mice | Zhou et al., 2010 | ||
| Myokines | |||||
| Myostatin | Muscle wasting | Cardiomyocyte-specific deletion of Myostatin and use of a myostatin blocking antibody | Heineke et al., 2010 | ||
| SerpinA3 | Tumor growth | MI/HTx in APCmin mice | Meijers et al., 2018 | ||
| Cachexokines | |||||
| Ataxin-10 | Cardiac atrophy | Tumor cell (MC38, C26, SW480) injection in mice, APC delta 580 mice | Schafer et al., 2016 | ||
| Insulin depletion | Cardiac wasting | Insulin supplementation | Thackeray et al., 2017 | ||
| MicroRNAs | |||||
| miR-145 | Cardiac fibrosis | miR-145 KO mice | Zhao et al., 2015 | ||
| Tumor growth | miR/miR inhibitor transfection | Xing et al., 2013 | |||
| miR transfection | Xia et al., 2014 | ||||
| miR-1 | Elevated in MI after LAD ligation | LAD ligation | D’Alessandra et al., 2010 | ||
| Tumor growth suppression | miR transfection | Liu et al., 2017 | |||
| miR-133a/b | Elevated in MI after LAD ligation | LAD ligation | D’Alessandra et al., 2010 | ||
| Heart malformations/DCM | miR-133a-1/2 dKO mice | Liu et al., 2008 | |||
| Tumor growth suppression | miR transfection | Qin et al., 2013 | |||
| miR-208a | AV blockage/cardiac hypertrophy | mR-208a Tg/KO mice | Callis et al., 2009 | ||
| Oncogene/Tumor proliferation | miR overexpression/miR siRNA | Li et al., 2014 | |||
| Metabolism | |||||
| Akt | Heart failure and mitochondrial dysfunction | Akt transgenic mice, constative active and inducible | Wende et al., 2015 | ||
| Enhanced glucose metabolism, GLUT-1 expression | Inducible Akt-transgenic mouse hepatoma cells | Barthel et al., 1999 | |||
| HK activity, HK-mitochondria interaction | Akt-1 KO, Akt-1/2 dKO | Majewski et al., 2004 | |||
| PGC-1α | Heart failure | PGC-1α KO mice | Arany et al., 2006 | ||
| PPCM | PGC-1α KO mice | Patten et al., 2012 | |||
| Apoptosis | Pancreatic Cancer Stem Cells/Metformin/MYC expression | Sancho et al., 2015 | |||
| Glycolytic flux and poor prognosis in breast cancer | Breast cancer cell lines/siRNA treatment | McGuirk et al., 2013 | |||
| O-GlcNAc | Cardiac Hypertrophy | Db/db mice | Marsh et al., 2011 | ||
| Heart failure | Db/db mice, STZ injections, HDAC4 KO mice | Kronlage et al., 2019 | |||
| Transient CMP | HDAC4 KO mice, STIM1/2 dKO mice | Lehmann et al., 2018 | |||
| Glycolytic flux/apoptosis | Breast cancer cell line/OGT-shRNA transfections | Ferrer et al., 2014 | |||
| Pancreas duct epithelial cells/OGT-shRNA transfections | Ma et al., 2013 | ||||
| Tumor growth | Xenograft models with shOGT | Caldwell et al., 2010 | |||
| Circulating metabolites | |||||
| D2-HG | Alterations in cardiac glucose utilization and epigenetic repression | IDH2R140Q-mutant mice | Karlstaedt et al., 2016 | ||
| Cardiotoxicity | AML patients with IDH1/2, iPS derived cardiomyocytes | Kattih et al., 2021 | |||
ActRIIB, Activin type 2 receptor; APC, Adenomatosis polyposis coli; AV, Atrioventricular; CHD, Coronary heart disease; CMP, Cardiomyopathy; CHO-cells, Chinese Hamster Ovarian cells; D2-HG, D-2-Hydroxyglutarate; DCM, Dilatative cardiomyopathy; dKO, Double Knockout; GLUT-1, Glucose transporter 1; HTx, Heart transplantation; HK, Hexokinase; HDAC4, Histon deacetylase 4; IFN-γ, Interferon-gamma; IL, Interleukin; IDH2, Isocitrate dehydrogenase 2; KO, Knockout; LAD, Left anterior descending coronary artery; Db/Db, Leptin receptor-deficient mouse line; miR, MicroRNA; Min, Multiple intestinal neoplasia; MI, Myocardial infarction; O-GlcNAc, O-Linked N-Acetylglucosamine; PPCM, Peripartum cardiomyopathy; PGC-1α, Peroxisome proliferator-activated receptor-gamma coactivator; OGT, Protein O-GlcNAc Transferase; Akt, Protein kinase B; shRNA, small hairpin RNA; siRNA, Small interfering RNA; STZ, Streptozotocin; STIM1/2, Stromal interaction molecule 1/2; TNF-α, Tumor necrosis factor alpha; Tg, Transgene; TGF-β, Tumor growth factor beta.