Cardiovascular diseases encompass the conditions that affect the heart and blood vessels. Beyond the major public-health challenges of hypertension, heart failure and atherosclerosis, research is moving towards an increasingly fine understanding of their molecular and genetic mechanisms, driven by regenerative medicine, gene therapy and new cellular models.
In this field, the work to which Inovarion has contributed focuses mainly on conditions with strong molecular determinism. A first group concerns genetic cardiomyopathies. In dilated cardiomyopathy linked to lamin A/C (LMNA) mutations, the laboratory studied the extracellular-matrix remodelling mediated by the LOXL2 enzyme and evaluated the antibody simtuzumab to preserve cardiac function[1], drawing on cardiomyocytes derived from induced pluripotent stem cells (hiPSCs) and engineered cardiac tissue.
Pulmonary arterial hypertension is the subject of other work, addressing the BMP9/BMP10 and ALK1 signalling pathways, which are decisive in pulmonary vascular remodelling and the resulting cardiac phenotypes, up to high-output heart failure[4].
Other work concerns the cardiovascular complications of pregnancy, in particular pre-eclampsia: the characterisation of the CORIN protein — a serine protease involved in blood-pressure regulation — overexpressed in the placenta[7], and the identification of genetic variants associated with risk, using machine-learning predictive approaches applied to pregnancy cohorts[6].
Finally, the cardiac involvement of muscular dystrophies has also been addressed: the role of the CD38/NAD+ axis in the dystrophic phenotype[5] and the inflammatory consequences on the myocardium of dystrophin-replacement therapies in Duchenne dystrophy[2], using mouse models of the disease.
This research mobilises advanced cellular models (hiPSC cardiomyocytes, engineered cardiac tissue), knock-out mouse models, transcriptomics, genotyping and machine learning, as well as placental explants. The combination of patient-derived cardiomyocytes and engineered cardiac tissue provides a particularly suitable platform for testing therapeutic hypotheses on human cardiac tissue, upstream of animal models. This work has appeared in leading specialist journals, including Circulation: Heart Failure, Cardiovascular Research and Arteriosclerosis, Thrombosis, and Vascular Biology.
This work thus sits at the intersection of molecular cardiology, genetics, rare diseases and reproductive medicine. By linking the gene to the tissue phenotype, from fundamental concept to translational validation, Inovarion supports demanding projects and places this expertise at its partners’ service.
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Representative publications
- Kervella et al. Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function in LMNA Mutation-Induced Dilated Cardiomyopathy. Circ Heart Fail, 2026. PubMed
- Forand et al. Long-Term Dystrophin Replacement Therapy in Duchenne Muscular Dystrophy Causes Cardiac Inflammation. JACC Basic Transl Sci, 2025. Record → · PubMed
- Malham et al. Intrinsic cancer cell phosphoinositide 3-kinase δ regulates fibrosis and vascular development in cholangiocarcinoma. Liver Int, 2023. Record → · PubMed
- Bouvard et al. Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10. Cardiovasc Res, 2022. Record → · PubMed
- Zélicourt et al. CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype. EMBO Mol Med, 2022. Record → · PubMed
- Liu et al. C1431T Variant of PPARγ Is Associated with Preeclampsia in Pregnant Women. Life (Basel), 2021. Record → · PubMed
- Degrelle et al. Placental Overexpression of Soluble CORIN in Preeclampsia. Am J Pathol, 2020. Record → · PubMed
- Cohen-Aubart et al. Hypoalphalipoproteinemia and BRAF(V600E) Mutation Are Major Predictors of Aortic Infiltration in the Erdheim-Chester Disease. Arterioscler Thromb Vasc Biol, 2018. Record → · PubMed