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Candidatures for WinningNormandy research training network

Our laboratory is welcoming applications from ambitious junior researchers with at least 4 years of research experience (including PhD studies) to apply for the competitive research funding from the postdoctoral research training network  The WINNINGNormandy Fellowship Programme | Région Normandie

Our laboratory is offering potential candidates a unique research environment, including  long-standing expertise in functional in vivo and ex vivo cardiovascular evaluations and access to our wide panel of relevant experimental models of cardiovascular diseases ranging from myocardial infarction, ischemia-reperfusion injury, chronic heart failure, acute heart failure, metabolic syndrome-induced cardiomyopathy, chronic kidney-disease induced cardiomyopathy, and sepsis-induced cardiomyopathy. Please contact our lead PIs for more details:

Paulus Mulder (expertise in HF models) paul.mulder[at] ORCID

Ebba Brakenhielm (expertise in cardiac lymphatics) ebba.brakenhielm[at] ORCID

Jeremy Bellien (expertise in endothelial dysfunction) jeremy.bellien[at] ORCID

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sEH blockade prevents cardiorenal syndrome

A recent experimental study, directed by D Guerrout, published in Front Mol Biosci , describes the beneficial cardiac impact, on both diastolic and systolic functions, of blocking soluble epoxide hydrolase (sEH) during chronic kidney disease (CKD) induced by 5/6 nephrectomy (Nx) in mice. These beneficial effects may be mediated by the prevention of endothelial dysfunction, independent from kidney preservation and antihypertensor effect. Thus, inhibition of sEH holds a therapeutic potential in preventing type 4 cardiorenal syndrome.

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Finerenone beneficial impact in ovariectomized mice

A recent study, directed by A Ouvrard-Pascaud, published in ESC Heart Failure describes the beneficial impact of Mineralocorticoid receptor blockade, with finerenone, on cardiac function and exercise capacity in ovariectomized mice. Briefly, the authors evaluated whether the non-steroidal mineralocorticoid receptor antagonist finerenone limited the progression of heart failure in ovariectomized (OVX) mice with metabolic disorders. They found that Finerenone improved mitochondrial ATP production in OVX mice. In addition, weight gain, increased blood pressure, and decreased insulin and glucose tolerance developing in OVX mice were improved by finerenone. The exercise capacity was diminished in untreated OVX mice and improved with Finerenone.

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BioArt 2020 winner

Coraline Heron, a 1st year PhD student in the laboratory, has together with our collaborator, David Godefroy (Inserm U1239), used light sheet imaging to reveal the delicate network of cardiac lymphatics in mice. Their work was awarded with a 1st Prize at the yearly FASEB BioArts competition in 2020.

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Use of RAS inhibitors in patients with COVID-19

Some concerns about the prescription of drugs acting on the renin-angiotensin system (RAS) have emerged due to SARS COV2 and COVID-19 pandemic and the revelation of the fundamental role of ACE2 (angiotensin-converting enzyme 2) in COVID-19 infection. Indeed, SARS COV2 utilizes ACE2 as a membrane receptor to enter target cells. Consequently, the question arises whether RAS modulating drugs impact the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection.  Here we discuss the evidence avilable on the impact of angiotensin-converting enzyme 1 inhibitors (ACEi) versus angiotensin II type 1 receptor blockers (ARB). Based on the currently available evidences, and as recommended by several medical societies, ACEi or ARB should not be systematically discontinued because to date no safety signal was raised with the use of these drugs.

Alexandre J, Cracowski JL, Richard V, Bouhanick B; French Society of Pharmacology and Therapeutics (SFPT). Drugs acting on renin angiotensin system and use in ill patients with COVID-19. Therapie. 2020;75(4):319-325.

doi: 10.1016/j.therap.2020.05.009.. PMID: 32553503

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Mechanisms of Acute Decompensation of Heart Failure

In a recent study from our laboratory, Pr Paul Mulder and colleagues have developed a new animal model of acute cardiac decompensation induced by salt overload. Using this model, they investigated whether heart rate reduction (HRR) opposes the acute decompensation‐related aggravation of cardiovascular dysfunction. Briefly, they found that acute HRR, induced by the If current inhibitor S38844, opposes cardiac decompensation by preventing aggravation of cardiovascular dysfunction, including reduced myocardial tissue perfusion and coronary relaxation. Importantly, the protective effects of HRR persist beyond the transient treatment, and led to partial prevention of the development of pulmonary congestion. Whether early transient HRR induced by If current inhibitors or other bradycardic agents, i.e. beta‐blockers, exerts beneficial effects in human ADHF warrants further investigation.

ESC Heart Failure

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Endothelium, Valvulopathy
& Heart Failure

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