Cardio-metabolic models and services

Offering in vivo and in vitro cardio-metabolic models to allow preclinical drug development for different etiologies

Our cardio-metabolic team is committed to delivering a range of high quality and validated in vitro and in vivo models for key cardio-metabolic disease (CMD) risk factors and etiologies. This selection allows drug developers to test therapeutic efficacy to prevent or reverse insulin resistance, pre-diabetes, type 2 diabetes, NASH/NAFLD and cardiovascular disease and heart failure (with model of both HFrEF and HFpEF). With high translatability of results, each model is customizable and can be executed in conjunction with many of our standard drug development services.  

Performing your cardio-metabolic research with InnoSer allows you to uncover valuable insights into the mode of action, pharmacokinetics, toxicity and efficacy of your lead compounds. We support your research with our highly skilled technical and scientific team members and generate reliable and relevant data sets with state-of-the-art technologies. The translational InnoSer histopathological services improve your chances of clinical success. 

Valuable aspects of InnoSer’s cardio-metabolic pipelines:

  • Selection of disease models that cover a variety of etiologies of cardio-metabolic disease
  • Centralized research with our full-service drug development options
  • Optimal study design and execution by experts
  • Specialized facilities and trained personnel equipped for reliable execution of technical cardiac surgeries and other technical procedures
  • A full suite of (digital) histopathology assessments

Cardio-metabolic Models Overview

Heart-Failure Models:

Myocardial Infarction

Myocardial infarction drug development model

Ischemic / Reperfusion

Myocardial infarction drug development model

Transverse Aortic Constriction

Myocardial infarction drug development model

Angiotensin II

angiotensin II Pump cardiac model

Diabetic Cardiomyopathy

western diet type 2 diabetes rat model

Metabolic Models:

Type 2 Diabetic Rat

western diet type 2 diabetes rat model

Type 1 Diabetes Models

type 1 diabetes mouse model

NASH model

NASH model

Find the right model for you. Download our cardio-metabolic leaflet and compare the model capabilities 

cardio-metabolic models for drug development leaflet preview

Cardio-metabolic research with InnoSer

cardiography - heart

Powered by imaging capabilities

Particularly in vivo imaging has become a valuable tool for collecting mid-study data in animal studies. These non-invasive methods can be applied with high sensitivity and in real-time. With InnoSer’s imaging capabilities measure a variety of functional cardiac readouts customizeable to your research outcomes. These readouts can include cardiac function, infarct size, heart tissue mass, and ejection fraction.

HE stain of heart tissue pathology readouts

Smart pathological assessment

Enhance the translational value of your cardio-metabolic research with a histopathological assessment of clinically relevant biomarkers. We can provide insights into inflammation, vascularization, hypertrophy and fibrosis using sound techniques and expert application. Supported by digital workflows for efficient and accurate results our histopathology services will see your research enhanced through technology. Read more >>

checking on the progress and breeding of in vivo models in the contract research organisation in Belgium

Fast study initiation with timely and insightful updates

Our cardio-metabolic models are initiated quickly and set up upon agreement with our dedicated cardio-metabolic study team. Timely updates enable you to closely follow the progression of your project and help inform and guide your research. We provide consulting on relevant endpoint analysis and help guide and inform your research with our expertise. 

Myocardial Infarction

We offer both mouse and rat models of cardiac ischemia induced by permanent ligation of the left anterior descending (LAD) coronary artery. Therapy initiation can be tailored to your drug candidate, including cell therapy delivery. Our technical experts are highly trained to perform the MI surgical procedures producing standardized and uniform infarction sizes to guarantee reliable therapeutic efficacy testing. This model is critical in the development of innovative treatments that target post infarction remodelling and cardiac tissue repair. Our myocardial infarction model combined with our range of readout options are designed to thoroughly assess your compounds or other advanced therapeutic treatment modalities cardioprotective effects and repair capabilities. Do not hesitate to ask about our team’s expertise in (stem) cell delivery. 

Key Model Readouts:

  • Ultrasound left ventricular function
  • Infarct size & area at risk
  • Cardiac remodeling analysis
  • Inflammation and scar formation

Ischemia / Reperfusion Model

Similar to our myocardial infarction model, this model of LAD ischemia/reperfusion is executed with our experts’ technical capabilities. This model is key to study cardio-protective effects, remodelling and regenerative effects of candidate drugs after ischemia / reperfusion. We offer tuneable ischemia times to meeting your research questions needs. 

Key Model Readouts:

  • Ultrasound left ventricular function
  • Infarct size & area at risk
  • Cardiac remodeling analysis
  • Inflammation and scar formation

Transverse Aortic Constriction

InnoSer offers a well-established transverse aortic constriction (TAC) mouse model as golden standard to study drug efficacy on cardiac hypertrophy and associated heart failure This pressure overload model allows for reliable and translatable results for drug development. Our TAC model shows clear cardiac remodeling with left ventricle dilation and hypertrophy and shows features of both HFrEF and HFpEF. 

Key Model Readouts:

  • Echocardiography left ventricular function 
  • Cardiac hypertrophy 
  • Fibrosis & remodelling

Angiotensin II Hypertension

Chronic angiotensin II (ANG II) infusion leads to progressive hypertension inducing renovascular remodelling and heart failure. By combining the InnoSer cardiology expertisewith our in–house nephrology capabilities, this model provides our clients with relevant and insightful data regarding the many wide-ranging effects of their compound in managing and influencing cardiac failure and kidney disease. This murine model for hypertension gives drug developers a platform to better understand their lead compounds therapeutic effects 

Key Model Readouts:

  • Ultrasound left ventricular function 
  • Heart remodeling & fibrosis 
  • Hypertrophy 
  • Kidney function

Diabetic / Cardiomyopathy Rat Model

Our Western diet rat model of type 2 diabetes and diabetic cardiomyopathy can be tailored to study prediabetes, type 2 diabetes and diabetic cardiomyopathy based on study duration. This is a predictive model to study drug efficacy in heart failure with preserved ejection fraction (HFpEF) with obesity and type 2 diabetes as key pathological causative risk factors. Rats develop progressive cardiac dysfunction as a result of a high–fat, high–sugar diet. Drug developers can rely on this model to assess their compound’s ability to prevent the diabetes induced cardiomyopathy or directly impact the varying symptoms of the cardiac dysfunction as a result of the western diet.

Key Model Readouts:

  • Ultrasound left ventricular function
  • Glucose tolerance
  • Metabolic profiling
  • Cardiac hypertrophy
  • Fibrosis & remodeling
HFpEF echocardiography table for cardiomyopathy mouse model

Type 1 diabetes mouse models

We support both chemically induced type 1 diabetes mouse models and studies in genetic models. Test your investigational therapy for effect on glycemic control and glucose tolerance in fast and golden standard experimental diabetes mouse models with full tailoring flexibility. Our team has extensive experience in beta cell replacement therapy testing including cellular encapsulation in microcapsules and macrodevices or islet kidney capsule transplantation.

Key Model Readouts:

  • Glucose monitoring
  • Insulin secretion
  • IPGTT, OGTT
  • Islet cell composition
  • In vitro insulin-secreted glucose secretion

NASH model

InnoSer offers a well validated and clinically translatable diet induced C57BL/6NTac Nonalcoholic steatohepatitis (NASH) model through Taconic. Animals are fed a modified Amylin liver NASH (AMLN) diet resulting in progressive obesity, fatty liver, liver inflammation and fibrosis. NASH animals show insulin resistance, robust steatosis, hepatic inflammation, hepatocyte ballooning and activated stellate cells. This model allows researchers to implement a broad range of histopathology readouts and relevant intermediate biomarkers for long-term follow-up.

Key Model Readouts:

  • Liver weight 
  • Liver inflammation & fibrosis histopathology 
  • Liver immune cell composition
  • Inflammatory cytokines

The people behind the models 

Leon de Windt

Prof. Dr. Leon de Windt

De Windt’s laboratory is interested in cardiac gene regulatory mechanisms by transcription factors and microRNAs that control pathological cardiac remodelling, an early step towards heart failure.

References

  • Bourajjaj M, Armand AS, da Costa Martins PA, Weijts B, van der Nagel R, Heeneman S, Wehrens XH, De Windt LJ. NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure. J Biol Chem. 2008 Aug 8;283(32):22295-303. doi: 10.1074/jbc.M801296200. Epub 2008 May 12. PMID: 18477567.
  • el Azzouzi H, Leptidis S, Bourajjaj M, Armand AS, van der Nagel R, van Bilsen M, Da Costa Martins PA, De Windt LJ. Peroxisome proliferator-activated receptor (PPAR) gene profiling uncovers insulin-like growth factor-1 as a PPARalpha target gene in cardioprotection. J Biol Chem. 2011 Apr 22;286(16):14598-607. doi: 10.1074/jbc.M111.220525. Epub 2011 Jan 18. PMID: 21245137; PMCID: PMC3077657.
  • Peters T, Hermans-Beijnsberger S, Beqqali A, Bitsch N, Nakagawa S, Prasanth KV, de Windt LJ, van Oort RJ, Heymans S, Schroen B. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice. PLoS One. 2016 Feb 26;11(2):e0150236. doi: 10.1371/journal.pone.0150236. PMID: 26919721; PMCID: PMC4769011.
  • Raso A, Dirkx E, Philippen LE, Fernandez-Celis A, De Majo F, Sampaio-Pinto V, Sansonetti M, Juni R, El Azzouzi H, Calore M, Bitsch N, Olieslagers S, Oerlemans MIFJ, Huibers MM, de Weger RA, Reckman YJ, Pinto YM, Zentilin L, Zacchigna S, Giacca M, da Costa Martins PA, López-Andrés N, De Windt LJ. Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure. Mol Ther. 2019 Mar 6;27(3):584-599. doi: 10.1016/j.ymthe.2018.11.011. Epub 2018 Nov 17. PMID: 30559069; PMCID: PMC6403487.
  • Raso A, Dirkx E, Sampaio-Pinto V, El Azzouzi H, Cubero RJ, Sorensen DW, Ottaviani L, Olieslagers S, Huibers MM, de Weger R, Siddiqi S, Moimas S, Torrini C, Zentillin L, Braga L, Nascimento DS, da Costa Martins PA, van Berlo JH, Zacchigna S, Giacca M, De Windt LJ. A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nat Commun. 2021 Aug 10;12(1):4808. doi: 10.1038/s41467-021-25211-4. Erratum in: Nat Commun. 2022 Aug 25;13(1):4977. PMID: 34376683; PMCID: PMC8355162.
  • Nilsson J, Hörnberg M, Schmidt-Christensen A, Linde K, Nilsson M, Carlus M, Erttmann SF, Mayans S, Holmberg D. NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis. Sci Rep. 2020 Dec 11;10(1):21778. doi: 10.1038/s41598-020-78688-2. PMID: 33311540; PMCID: PMC7732838.
  • Deluyker D, Ferferieva V, Driesen RB, Verboven M, Lambrichts I, Bito V. Pyridoxamine improves survival and limits cardiac dysfunction after MI. Sci Rep. 2017 Nov 22;7(1):16010. doi: 10.1038/s41598-017-16255-y. PMID: 29167580; PMCID: PMC5700185.
  • Evens L, Beliën H, D’Haese S, Haesen S, Verboven M, Rummens JL, Bronckaers A, Hendrikx M, Deluyker D, Bito V. Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair? Int J Mol Sci. 2021 Aug 27;22(17):9266. doi: 10.3390/ijms22179266. PMID: 34502175; PMCID: PMC8431115.
  • Verboven M, Cuypers A, Deluyker D, Lambrichts I, Eijnde BO, Hansen D, Bito V. High intensity training improves cardiac function in healthy rats. Sci Rep. 2019 Apr 4;9(1):5612. doi: 10.1038/s41598-019-42023-1. PMID: 30948751; PMCID: PMC6449502.
  • Verboven M, Deluyker D, Ferferieva V, Lambrichts I, Hansen D, Eijnde BO, Bito V. Western diet given to healthy rats mimics the human phenotype of diabetic cardiomyopathy. J Nutr Biochem. 2018 Nov;61:140-146. doi: 10.1016/j.jnutbio.2018.08.002. Epub 2018 Aug 21. PMID: 30245335.

AAALAC Accreditation

InnoSer has earned the AAALAC accreditation, demonstrating our commitment to responsible animal care and use. AAALAC International is a nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. Our accreditation is valid for three years, incl. 2023. Read more about the AAALAC accreditation programme here.

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Animal Welfare

The 3Rs impact everything from policy and regulatory change to the development and uptake of new technologies and approaches. This is why Innoser has ongoing commitment and monitoring of these processes. The steps we practice maximize our ability to replace, reduce and refine animal involvement and facilitate our commitment to these principles when it comes to research and drug development.

Related Resources

Facility Management

Mouse Models Overview

Introducing InnoSer's Acceleration Program (ISAP)

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