Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized. We explored whether the expansion of cardiac fibroblasts after MI can be regulated through a paracrine action of cardiac stromal cells. METHODS: We performed a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of candidates were subsequently analyzed in mouse and human hearts and plasmas. The relationship between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-segment-elevation MI and serial cardiac magnetic resonance imaging evaluations. RESULTS: Cardiac stromal PW1+ cells undergo a change in paracrine behavior after MI, and the conditioned media from these cells induced a significant increase in the proliferation of fibroblasts. We identified a total of 12 candidates as secreted proteins overexpressed by cardiac PW1+ cells after MI. Among these factors, GDF3 (growth differentiation factor 3), a member of the TGF-ß (transforming growth factor-ß) family, was markedly upregulated in the ischemic hearts. Conditioned media specifically enriched with GDF3 induced fibroblast proliferation at a high level by stimulation of activin-receptor-like kinases. In line with the secretory nature of this protein, we next found that GDF3 can be detected in mice and human plasma samples, with a significant increase in the days after MI. In humans, higher GDF3 circulating levels (measured in the plasma at day 4 after MI) were significantly associated with an increased risk of adverse remodeling 6 months after MI (adjusted odds ratio, 1.76 [1.03-3.00]; P=0.037), including lower left ventricular ejection fraction and a higher proportion of akinetic segments. CONCLUSIONS: Our findings define a mechanism for the profibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling after MI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01113268.

T-cell dysregulation and inflammatory process in Gcn2 (Eif2ak4-/-)-deficient rats in basal and stress conditions.

Hereditary pulmonary veno-occlusive disease (hPVOD) is a severe form of autosomal recessive pulmonary hypertension and is due to biallelic loss of function of the EIF2AK4 gene (alias GCN2) coding for GCN2. GCN2 is a stress kinase that belongs to the integrated stress response pathway (ISR). Three rat lines carrying biallelic Gcn2 mutation were generated and found phenotypically normal and did not spontaneously develop a PVOD-related disease. We submitted these rats to amino acid deprivation to document the molecular and cellular response of the lungs and to identify phenotypic changes that could be involved in PVOD pathophysiology. Gcn2-/- rat lungs were analyzed under basal conditions and 3 days after a single administration of PEG-asparaginase (ASNase). Lung mRNAs were analyzed by RNAseq and single-cell RNAseq (scRNA-seq), flow cytometry, tissue imaging, and Western blots. The ISR was not activated after ASNase treatment in Gcn2-/- rat lungs, and apoptosis was increased. Several proinflammatory and innate immunity genes were overexpressed, and inflammatory cells infiltration was also observed in the perivascular area. Under basal conditions, scRNA-seq analysis of Gcn2-/- rat lungs revealed increases in two T-cell populations, a LAG3+ T-cell population and a proliferative T-cell population. Following ASNase administration, we observed an increase in calprotectin expression involved in TLR pathway activation and neutrophil infiltration. In conclusion, under basal and asparagine and glutamine deprivation induced by asparaginase administration, Gcn2-/- rats display molecular and cellular signatures in the lungs that may indicate a role for Gcn2 in immune homeostasis and provide further clues to the mechanisms of hPVOD development.

[Collaboration in home care: first interprofessional ambulatory proximity network]. / Collaboration dans les soins à domicile : un réseau interprofessionnel ambulatoire de proximité.

While interprofessionality is indispensable to respond to home care current issues, its implementation in the practice is a real challenge. The Genevan domiciliary model (reference by a nurse, targeted areas of interventions, etc.) needs to integrate all the resources of proximity. For this purpose, an interprofessional ambulatory and of proximity care network (RIAP) was created, aiming at strengthening the exchanges physicians/nurses about shared patients. RIAP benefits from an encouraging first assessment. Learnings from this experience are used to refine the modeling of this type of proximity network.

Alors que l'interprofessionnalité est indispensable pour répondre aux enjeux actuels du maintien à domicile, sa mise en œuvre dans la pratique représente un véritable défi. Le modèle domiciliaire genevois actuel (référence infirmière, zones d'interventions ciblées, etc.) nécessite d'intégrer toutes les ressources de proximité. Pour ce faire, un réseau de soins interprofessionnel ambulatoire de proximité (RIAP) a été créé, visant au renforcement de l'interprofessionnalité et résolument ancré dans la proximité des différents acteurs. Le RIAP repose notamment sur la consolidation des échanges médecins/infirmières autour de patients communs. Le premier bilan du RIAP est encourageant. Les apprentissages tirés de cette expérience permettent d'affiner la modélisation de ce type de réseau de proximité.

[COGERIA: coordination of care for the frail elderly]. / COGERIA : Coordination des soins de la personne âgée fragile.

COGERIA, a cantonal program is the fruit of a close collaboration between the Geneva General Directorate of Health and the major health and social partners in the canton. The program aims to improve inter-professional care for the frail elderly and to adapt their care pathways in close collaboration with their primary care physicians and home healthcare providers. Launched in May 2019, the program includes more than 283 beneficiaries and 152 primary care physicians in collaboration with the home healthcare providers in the Servette and Meyrin areas. Preliminary results show a possible trend towards a decrease in hospitalizations, as well as major satisfaction from beneficiaries and the COGERIA partners.

La Coordination des soins de la personne âgée fragile est un dispositif cantonal né d'une étroite collaboration entre la Direction générale de la santé et les grands partenaires de la santé et du social à Genève. Ce dispositif œuvre à améliorer la prise en charge interprofessionnelle autour des personnes âgées fragiles et à adapter leurs parcours de soins, en étroite collaboration avec les médecins traitants et les prestataires de soins à domicile. Lancé en mai 2019, le dispositif compte plus de 283 personnes incluses, avec 152 médecins traitants du réseau primaire en collaboration avec l'Institution genevoise de maintien à domicile, ainsi qu'une ouverture récente à tous les prestataires de soins dans les zones de la Servette et de Meyrin. Des résultats préliminaires mettent en évidence une possible tendance à une baisse d'hospitalisations ainsi qu'une grande satisfaction de la part des bénéficiaires et des partenaires.

Comparison of Human and Experimental Pulmonary Veno-Occlusive Disease.

Pulmonary veno-occlusive disease (PVOD) occurs in humans either as a heritable form (hPVOD) due to biallelic inactivating mutations of EIF2AK4 (encoding GCN2) or as a sporadic form in older age (sPVOD). The chemotherapeutic agent mitomycin C (MMC) is a potent inducer of PVOD in humans and in rats (MMC-PVOD). Here, we compared human hPVOD and sPVOD, and MMC-PVOD pathophysiology at the histological, cellular, and molecular levels to unravel common altered pathomechanisms. MMC exposure in rats was associated primarily with arterial and microvessel remodeling, and secondarily by venous remodeling, when PVOD became symptomatic. In all forms of PVOD tested, there was convergent GCN2-dependent but eIF2α-independent pulmonary protein overexpression of HO-1 (heme oxygenase 1) and CHOP (CCAAT-enhancer-binding protein [C/EBP] homologous protein), two downstream effectors of GCN2 signaling and endoplasmic reticulum stress. In human PVOD samples, CHOP immunohistochemical staining mainly labeled endothelial cells in remodeled veins and arteries. Strong HO-1 staining was observed only within capillary hemangiomatosis foci, where intense microvascular proliferation occurs. HO-1 and CHOP stainings were not observed in control and pulmonary arterial hypertension lung tissues, supporting the specificity for CHOP and HO-1 involvement in PVOD pathobiology. In vivo loss of GCN2 (EIF2AK4 mutations carriers and Eif2ak4-/- rats) or in vitro GCN2 inhibition in cultured pulmonary artery endothelial cells using pharmacological and siRNA approaches demonstrated that GCN2 loss of function negatively regulates BMP (bone morphogenetic protein)-dependent SMAD1/5/9 signaling. Exogenous BMP9 was still able to reverse GCN2 inhibition-induced proliferation of pulmonary artery endothelial cells. In conclusion, we identified CHOP and HO-1 inhibition, and BMP9, as potential therapeutic options for PVOD.

[Assessing frailty in care practices†: quick reminders in the light of the Covid-19 pandemic]. / Évaluer la fragilité dans les pratiques de soins†: brefs rappels à la lumière de la pandémie de Covid-19.

The Covid-19 pandemic has brought the concept of frailty back to the centre of debate, particularly for its relevance as a determinant of health outcomes. Frailty is concept that has long been a used gerontology. Today, several theoretical models of frailty are proposed in the literature, with as many tools to operationalize it. This article provides a brief outline of the three main models of frailty and the corresponding measurement instruments. The choice of the model as well as the choice of the assessment tool are discussed in the light of the clinical objectives pursued by health professionals. More generally, this article highlights the value of assessing frailty in routine practice to determine health outcomes and adapt care to individual needs.

La pandémie de Covid-19 a ramené le concept de fragilité au centre des débats, notamment pour son intérêt dans l'évaluation du pronostic en santé dans un contexte de menace sanitaire. La fragilité est un concept reconnu en gérontologie de longue date. Aujourd'hui, plusieurs modèles théoriques de la fragilité sont proposés dans la littérature, avec autant d'instruments permettant de l'opérationnaliser. Cet article propose un bref rappel des trois principaux modèles de fragilité ainsi que des instruments de mesure correspondants et de les discuter en fonction des objectifs cliniques poursuivis par les professionnels de la santé. Plus généralement, cet article souligne l'intérêt d'évaluer la fragilité dans une pratique de routine pour déterminer le pronostic de santé et adapter les soins aux besoins des individus.

Written interprofessional communication in the context of home healthcare: A qualitative exploration of Swiss perceptions and practices.

The aim of this study was to explore the practices and perceptions of Swiss home care professionals with regards to written interprofessional communication. We analyzed 11 home care notebooks and conducted six focus groups with home health-care professionals in 2015-2016. Interprofessional written communication was rarely explicit. Health professionals reported a lack of clarity about what to document and for whom. They felt unsure how to reconcile the need for confidential information-sharing among health professionals and the desire for patient/families' active involvement. An ideal (electronic) tool should allow patients to formulate goals and use the platform while allowing health professionals to communicate confidentially among themselves in order to avoid information retention.

A metabolic engineering strategy for producing conjugated linoleic acids using the oleaginous yeast Yarrowia lipolytica.

Conjugated linoleic acids (CLAs) have been found to have beneficial effects on human health when used as dietary supplements. However, their availability is limited because pure, chemistry-based production is expensive, and biology-based fermentation methods can only create small quantities. In an effort to enhance microbial production of CLAs, four genetically modified strains of the oleaginous yeast Yarrowia lipolytica were generated. These mutants presented various genetic modifications, including the elimination of ß-oxidation (pox1-6∆), the inability to store lipids as triglycerides (dga1∆ dga2∆ are1∆ lro1∆), and the overexpression of the Y. lipolytica ∆12-desaturase gene (YlFAD2) under the control of the constitutive pTEF promoter. All strains received two copies of the pTEF-oPAI or pPOX-oPAI expression cassettes; PAI encodes linoleic acid isomerase in Propionibacterium acnes. The strains were cultured in neosynthesis or bioconversion medium in flasks or a bioreactor. The strain combining the three modifications mentioned above showed the best results: when it was grown in neosynthesis medium in a flask, CLAs represented 6.5% of total fatty acids and in bioconversion medium in a bioreactor, and CLA content reached 302 mg/L. In a previous study, a CLA degradation rate of 117 mg/L/h was observed in bioconversion medium. Here, by eliminating ß-oxidation, we achieved a much lower rate of 1.8 mg/L/h.

Félix Voisin and the genesis of abnormals.

This article traces the genealogy of the category of 'abnormals' in psychiatry. It focuses on the French alienist Felix Voisin (1794-1872) who played a decisive role in the creation of alienist knowledge and institutions for problem children, criminals, idiots and lunatics. After a presentation of the category of 'abnormals' as understood at the end of the nineteenth century, I identify in the works of Voisin a key moment in the concept's evolution. I show how, based on concepts borrowed from phrenology and applied first to idiocy, Voisin allows alienism to establish links between the medico-legal (including penitentiary) and medical-educational fields (including difficult childhood). I stress the extent to which this enterprise is related to Voisin's humanism, which claimed to remodel pedagogy and the right to punish on the anthropological particularities of individuals, in order to improve them.

The use of lipofilling to treat congenital hypoplastic breast anomalies: preliminary experiences.

BACKGROUND: Treatment options for congenital hypoplastic breast anomalies are often open, including radial scoring, parenchymal flaps, and insertion of expanders and implants. Drawbacks of open techniques involve scarring, the use of drains, and inpatient stays. The use of lipofilling to treat breast deformities is increasing, as more research is completed in this area. PATIENTS AND METHODS: We report a retrospective study of 10 patients below the age of 20 following autologous fat transfer between January 1, 2003 and January 1, 2004. (2 Poland syndrome, 3 bilateral tuberous breast, and 5 unilateral micromastia). Age, cup size, the number of sessions, time interval between each session, volumes injected, and complications were recorded. Postoperative mammography, ultrasonography, and MRI were assessed by a specialized radiologist. Patients answered a questionnaire 1 year after the procedure. RESULTS: Mean follow-up was 68 months (60-77 months) and mean age was 17.5 years (15-20 years). Mean number of fat injection sessions was 2 (1-4) and mean volume injected 285 mL per breast (200-500 mL). The time interval between each session was 5 months (3-6 months). Cup size remained unchanged after at least 5 years of follow-up. One case underwent a contralateral breast reduction. The cosmetic results considered satisfactory in almost all the patients after 1 year of follow-up. None of our patients complained of scars or defects at the donor site. All breasts imaging were normal except 1 patient with oil cysts. CONCLUSION: Our preliminary results using lipofilling to treat young patients with breast hypoplasia with lipofilling are very encouraging. The authors believe it is an alternative of choice for the correction of the young woman's breast deformities if the avoidance of scarring is preferred.

The microalga Volvox carteri as a cell supportive building block for tissue engineering.

Background: V. carteri f. nagariensis constitutes, in its most simplified form, a cellularized spheroid built around and stabilised by a form of primitive extracellular matrix (ECM). Methods: We developed a modular approach to soft tissue engineering, by compact stacking V. carteri-based building blocks. This approach is made possible by the structure and cell adhesive properties of these building blocks, which results from the composition of their algal ECM. Results: A primary biocompatibility assessment demonstrated the cytocompatibility of the algal suspension, its histogenesis-promoting properties, and that it did not induce an inflammatory response in vitro. These results allowed us to consider the use of this algal suspension for soft tissue augmentation, and to initiate an in vivo biocompatibility study. V. carteri exhibited cellular fate-directing properties, causing (i) fibroblasts to take on an alkaline phosphatase+ stem-cell-like phenotype and (ii) both human adipose-derived stem cells and mouse embryonic stem cells to differentiate into preadipocytes to adipocytes. The ability of V. carteri to support histogenesis and adipogenesis was also observed in vivo by subcutaneous tissue augmentation of athymic mice, highlighting the potential of V. carteri to support or influence tissue regeneration. Conclusions: We present for the first time V. carteri as an innovative and inspiring biomaterial for tissue engineering and soft tissue regeneration. Its strategies in terms of shape, structure and composition can be central in the design of a new generation of bio-inspired heterogeneous biomaterials recapitulating more appropriately the complexity of body tissues when guiding their regeneration.

[Race and medicine]. / Race et médecine: une vieille histoire.

In this article, I argue that the problematic of "race and medicine", which has been the object of many recent debates, has a long history that it may be useful to understand better. I show more specifically that, from the very first uses of the concept of "race" in natural history during the XVIII(th) century, medical concepts and analogies served as important models. These medical models were especially useful to analyze "races" as alterations from an original identity. Different analogies are studied here. 1. The analogy between races' peculiar temperaments and morbid alterations of human constitution. 2. The analogy between the transmission of the alterations along generations and hereditary diseases. In this second analogy, I differentiate between two models: the degeneration of the human type and the transmission of a molecular alteration of one character.

Renal toxicity and biokinetics models after repeated uranium instillation.

During nuclear fuel processing, workers can potentially be exposed to repeated inhalations of uranium compounds. Uranium nephrotoxicity is well documented after acute uranium intake, but it is controversial after long-term or protracted exposure. This study aims to analyze the nephrotoxicity threshold after repeated uranium exposure through upper airways and to investigate the resulting uranium biokinetics in comparison to reference models. Mice (C57BL/6J) were exposed to uranyl nitrate (0.03-3 mg/kg/day) via intranasal instillation four times a week for two weeks. Concentrations of uranium in urines and tissues were measured at regular time points (from day 1 to 91 post-exposure). At each exposure level, the amount of uranium retained in organs/tissues (kidney, lung, bone, nasal compartment, carcass) and excreta (urine, feces) reflected the two consecutive weeks of instillation except for renal uranium retention for the highest uranium dose. Nephrotoxicity biomarkers, KIM-1, clusterin and osteopontin, are induced from day 4 to day 21 and associated with changes in renal function (arterial fluxes) measured using non-invasive functional imaging (Doppler-ultrasonography) and confirmed by renal histopathological analysis. These results suggest that specific biokinetic models should be developed to consider altered uranium excretion and retention in kidney due to nephrotoxicity. The threshold is between 0.25 and 1 mg/kg/day after repeated exposure to uranium via upper airways.

Physically Violent Parental Practices: A Cross-Cultural Study in Cameroon, Switzerland, and Togo.

Violence against children and adolescents is a widespread problem. However, most studies conducted in this field has been carried out in Western countries and studies are needed in non-Western countries, especially in Sub-Saharan Africa, where rates of child physical violence are high. The present study aimed firstly to document the different forms of physical violence and attitudes toward corporal punishment (CP) across Cameroon, Switzerland, and Togo. The second objective aimed, on the one hand, to understand the influence of cultural context, childhood physical abuse, and parental attitudes on physically violent parental practices in these three different cultural contexts. On the other, this study aimed to investigate the mediating role of childhood physical abuse and parental attitudes on the effect of cultural contexts on parental practices. Five hundred and forty-seven parents from Togo, Cameroon, and Switzerland filled out questionnaires concerning violent parental practices (ICAST-P), childhood physical abuse (CTQ-SF), and parental attitudes in favor of CP. Firstly, results highlighted some cultural differences regarding parental attitudes and practices. Secondly, the hierarchical regression showed that physical violence could be partially predicted by the cultural context, childhood abuse, and attitudes in favor of CP. Finally, childhood abuse and parental attitudes mediated the link between the cultural context and parental practices. This study underscores the importance of considering the cultural context when examining parental practices. Moreover, these results provide a better understanding of these types of parental practices in less studied contexts.

Cellulosic/Polyvinyl Alcohol Composite Hydrogel: Synthesis, Characterization and Applications in Tissue Engineering.

The biomedical field still requires composite materials for medical devices and tissue engineering model design. As part of the pursuit of non-animal and non-proteic scaffolds, we propose here a cellulose-based material. In this study, 9%, 18% and 36% dialdehyde-functionalized microcrystalline celluloses (DAC) were synthesized by sodium periodate oxidation. The latter was subsequently coupled to PVA at ratios 1:2, 1:1 and 2:1 by dissolving in N-methyl pyrrolidone and lithium chloride. Moulding and successive rehydration in ethanol and water baths formed soft hydrogels. While oxidation effectiveness was confirmed by dialdehyde content determination for all DAC, we observed increasing hydrolysis associated with particle fragmentation. Imaging, FTIR and XDR analysis highlighted an intertwined DAC/PVA network mainly supported by electrostatic interactions, hemiacetal and acetal linkage. To meet tissue engineering requirements, an interconnected porosity was optimized using 0-50 µm salts. While the role of DAC in strengthening the hydrogel was identified, the oxidation ratio of DAC showed no distinct trend. DAC 9% material exhibited the highest indirect and direct cytocompatibility creating spheroid-like structures. DAC/PVA hydrogels showed physical stability and acceptability in vivo that led us to propose our DAC 9%/PVA based material for soft tissue graft application.

Enhancement of the denitrification performance of an activated sludge using an electromagnetic field in batch mode.

The influence of electromagnetic fields on bacterial denitrification has been tested on synthetic media with sludges from wastewater treatment stations, in batch mode. The effects of the intensity of the magnetic induction ratio B (mT), reaction volume and initial biomass concentration on the kinetics of the denitrification process were studied. Magnetic field had both an optimal stimulating effect on the activity of the denitrifying flora for B (mT)/mgx values of the order of 0.212, and an inhibitory effect for the values beyond the latter.Sludges underwent multiple exposure cycles to magnetic fields. It was shown that, after three exposure cycles, denitrification kinetics went from 6.5 to 12.7 mg N-NO-3.L-1.h-1 which corresponds to a 2.7 fold improvement. The improved performance persists even after the cessation of the magnetic field. Observation of the sludge by the environmentalelectron microscope shows that the microbial population forming the starting sludge; changed following exposure to the magnetic field. The action of the; electromagnetic field on the microbial populations in denitrification resulted in the modification of the diversity of the flora that is initially present, favoring the development of Proteo bacteria, particularly the Betaproteo bacteria subclass, which results in improved denitrification.

Monitoring the impact of hydrocarbon contamination and nutrient addition on microbial density, activity, and diversity in soil.

The development of optimal in situ bioremediation strategies requires a better knowledge of their impact on the soil microbial communities. We have evaluated the impact of hexadecane contamination and different nutrient amendments on soil microbial density and activity. Microbial density was measured via total DNA quantification, and microbial activity via respiration and RNA variation. The RNA/DNA ratio was also determined, as it is a potential indicator of microbial activity. PCR-amplified 16S rRNA genes were cloned and sequenced to analyze the diversity of bacterial communities. Nutrient addition significantly increased respiration and DNA and RNA concentrations in contaminated soil, indicating a limitation of degradation and growth by the availability of nitrogen and phosphorus in unamended microcosms. Hexadecane treatment slightly affected the diversity of the bacterial community, while it was dramatically reduced by nutrient treatments, particularly the addition of nitrogen and phosphorus. Microbial community composition was also altered with the enrichment of populations related to Nocardia in bioremediated soils, while uncultured Proteobacteria were mostly detected in uncontaminated soil.

[Body contouring surgery]. / Chirurgie de la silhouette.

Body contouring after massive weight loss is an important step of the treatment for obese and overweight patients. As a member of the bariatric multidisciplinary team, the plastic surgeon helps to finish the reconstruction process by removing skin and fat excess. With the rise of bariatric surgery and extreme weight loss, this surgery is more in demand and has became more and more performed recently and well codified. Over the last decade, surgical techniques have dramatically changed allowing providing safe procedures and harmonious results. Lower body lift surgery (also known as a belt lipectomy) allows to treat safely contour deformities of the abdomen, the thigh and the buttocks resulting from massive weight loss. The result will be harmonious because the treatment is circumferential.

[Surgical treatment of lipodystrophy]. / Chirurgie des lipodystrophies.

With the introduction of highly active antiretroviral therapy HIV has become a chronic but not necessarily a life-threatening disease. One drawback of the medication is the lipodystrophy syndrome that develops. Its precise mechanisms underlying are not well understood. The syndrome includes peripheral fat wasting (e.g. face, buttocks) and central fat accumulation. This condition can be very distressing to the patient who may be depressed and lose self-esteem which eventually leads to social withdrawal. The facial lipoatrophy is often experienced as the main problem as it is a social stigma telling other people that the patient is infected with HIV. The second zone bothering these patients is the buttocks. Buttocks lipoatrophy constitutes both an esthetic problem as well as a functional problem causing pain on sitting and even on walking.

Anti-integrin αv therapy improves cardiac fibrosis after myocardial infarction by blunting cardiac PW1+ stromal cells.

There is currently no therapy to limit the development of cardiac fibrosis and consequent heart failure. We have recently shown that cardiac fibrosis post-myocardial infarction (MI) can be regulated by resident cardiac cells with a fibrogenic signature and identified by the expression of PW1 (Peg3). Here we identify αV-integrin (CD51) as an essential regulator of cardiac PW1+ cells fibrogenic behavior. We used transcriptomic and proteomic approaches to identify specific cell-surface markers for cardiac PW1+ cells and found that αV-integrin (CD51) was expressed in almost all cardiac PW1+ cells (93% ± 1%), predominantly as the αVß1 complex. αV-integrin is a subunit member of the integrin family of cell adhesion receptors and was found to activate complex of latent transforming growth factor beta (TGFß at the surface of cardiac PW1+ cells. Pharmacological inhibition of αV-integrin reduced the profibrotic action of cardiac PW1+CD51+ cells and was associated with improved cardiac function and animal survival following MI coupled with a reduced infarct size and fibrotic lesion. These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of αV-integrin could reduce pathological outcomes following cardiac ischemia.