Annexins and cardiovascular diseases: Beyond membrane trafficking and repair

Sebastian-Jaraba, Irene San; Blázquez-Serra, Rafael; Martı́n-Ventura, José Luis; Blanco-Colio, Luis Miguel

doi:10.3389/fcell.2022.1000760

Cited by 13 publications

(9 citation statements)

References 163 publications

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“…One main marker of these fetal delineating/epimysial fibroblasts is ANXA2 . ANXA2 has been shown to be associated with membrane repair, cell-to-cell contact, membrane ruffling and cytoskeletal scaffolding (Lim and Hajjar, 2021; Méndez-Barbero et al, 2022), consistent with a function in maintaining/constraining muscle size. Moreover, ANXA2 partner proteins, such as the scaffold protein AHNAK2 (Pascal et al, 2022) and the Ca 2+ -binding protein S100A6 (Cheng et al, 2005), are also markers of delineating fibroblasts.…”

Section: Discussionmentioning

confidence: 94%

Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

Hirsinger,

Blavet,

Bonnin

et al. 2024

Preprint

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Tight developmental coordination of muscle attachments with skeletal muscle is fundamental for building functional limbs and allowing locomotion. Muscle attachments include connective tissue fibroblasts of tendon and muscle connective tissue. Although muscle attachments play critical roles in development, our understanding of connective tissue fibroblast developmental programs lags behind that of other components of the musculoskeletal system, mainly because fibroblasts are highly heterogeneous and poorly characterized. Combining single-cell RNA-sequencing-based strategies including trajectory inference andin situhybridization analyses, we address the diversity of connective tissue fibroblasts and their developmental trajectories during chicken limb fetal development. We show that fibroblasts switch from a program providing positional information to a program of lineage diversification at the onset of fetal period. Muscle connective tissue and tendon contain several fibroblast populations that emerge asynchronously. Once the final muscle pattern is set,in silicofibroblast populations that are close in transcriptional identity are found in neighbouring locations in limbs, prefiguring the adult fibroblast layers associated to muscle. We propose that the limb connective tissue is organised in a continuum of promiscuous fibroblast identities, allowing for the robust and efficient connection of the muscular system to bone and skin.HighlightsDissection of connective tissue heterogeneity using single-cell RNA-sequencing andin situRNA stainingIn silicofibroblast populations map to distinct fibroblast layers in limbsMolecular signatures of fetal fibroblast populations at the origin of limb adult connective tissueEpimysium and endomysium fibroblasts are transcriptionally distinct at fetal stageLimb fibroblasts display promiscuous identities reflecting their interconnected 3D-networkFibroblasts switch from providing positional information to differentiation during development

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Section: Discussionmentioning

confidence: 94%

Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

Hirsinger,

Blavet,

Bonnin

et al. 2024

Preprint

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“…It is possible that such changes are the result of anti-apoptotic activity of GRP78 recently revealed in an ischemia-reperfusion model [32]. In case of long-term hypoxia, there was found a 2-fold increase in AN concentration compared to control, which is a sign of death of a substantial number of cells and, possibly, the onset of cardiac myogenic dilatation development [33].…”

Section: Original Researchmentioning

confidence: 90%

Left ventricular remodeling in normotensive Wistar rats exposed to intermittent hypoxia of different duration

Kolesnyk¹,

Kolesnyk²,

Hancheva

et al. 2023

Patologìâ

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Intermittent hypoxia has been studied for many years as a promising non-pharmacological method of cardiovascular disease prevention. Hypoxic effects are accompanied by structural and functional changes in the myocardium. There is a direct link between the duration of hypoxic exposures and the severity of left ventricular myocardial remodeling. A range of histochemical markers of myocardial remodeling (cardiotrophin-1, titin, collagen type 1, annexin V) characterizing parenchymal-stromal relationships in the myocardium has shown high informativeness and prognostic value. The aim of the study was to examine cardiotrophin-1, titin, collagen type 1, annexin V and the morphofunctional state of the left ventricle of the heart in experimental rats exposed to intermittent 15-day (IH15) and 60-day hypoxia (IH60). Materials and methods. Intermittent hypoxia was modeled using 30 normotensive male Wistar rats, 7–8 months old, which were randomly assigned to 3 experimental groups of 10 animals each: 1) INT – a control group – intact animals (196.3 ± 6.8 g); 2) IH15 – 15-day hypoxia (205.6 ± 4.1 g); 3) IH60 – 60-day hypoxia (201.1 ± 5.5 g). The study compared the effects of intermittent hypoxia of varying duration: 15-day and 60-day hypoxia. Experimental modeling of intermittent hypoxia of 2 terms revealed a number of differences between the effects dependent on this factor duration through functional (blood pressure measurement, echocardiography) and immunofluorescent studies. Results. Blood pressure in rats of both groups was in the normotensive range, but an increase in systolic by 10 % and diastolic by 19 % was found in IH60 group compared to IH15 group (p < 0.05). In IH15 group, there was a significant decrease in end-diastolic dimension by 20 %, end-systolic dimension by 22 %, an increase in the thickness of left ventricular posterior wall by 44 % and interventricular septum by 33 % as well as left ventricular mass by 12 %, indicating concentric remodeling of the left ventricle, the development of which was confirmed by a 76 % increase in relative wall thickness compared to that in the control group (p < 0.05). Along with these changes, a decrease in end-diastolic volume by 47 %, end-systolic volume by 48 %, stroke volume by 49 % and cardiac output by 50 % with preserved ejection fraction was revealed (p < 0.05). While the parameters of IH60 rats were characterized by an increase in the thickness of interventricular septum by 33 % and left ventricular posterior wall by 17 %, as well as left ventricle mass by 23 %, relative left ventricular wall thickness was 15 % higher than the control value (p < 0.05). At the same time, diastolic volume was 9 % decreased and systolic volume was 24 % increased (p < 0.05). Also, cardiac output was increased by 58 % compared to that in 15-day hypoxic rats with an 8 % decrease in ejection fraction (p < 0.05). The concentrations of markers in IH60 group exceeded those in IH15, namely: cardiotrophin-1 by 39 %, titin by 70 %, collagen type 1 by 60 % and annexin V by 130 % (p < 0.05). Conclusions. 15-day hypoxia forms concentric left ventricular hypertrophy according to echocardiography findings; the study of marker profile of myocardial remodeling has revealed the development of moderate hypertrophy with increased resilient-elastic properties and decreased intensity of cardiomyocyte death. Remodeling caused by 60-day hypoxia is characterized by the eccentric pattern of changes with severe hypertrophy, significant fibrosis associated with apoptosis of cardiomyocytes. Such morphofunctional state of the myocardium may indicate the initial stages of maladaptation, increasing the risk of heart failure development.

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“…NTRK fusion partners usually contribute a dimerization domain [31]. It is plausible that the annexin repeats retained in the fusion drive localization of the fusion protein to the plasma membrane [32] and promote dimerization to activate the kinase domain of NTRK.…”

Section: Discussionmentioning

confidence: 99%

Entrectinib for NTRK Fusion-Positive Metastatic Melanoma Progressing on Combined PD-1 and CTLA-4 Inhibition: A Case Report

Dawood,

Ali

2023

Case Rep Oncol

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Introduction: The burden of melanoma is increasing globally. Despite the use of immunotherapy and targeted therapy, the prognosis of metastatic melanoma remains relatively poor. The integration of comprehensive molecular profiling can lead to the detection of actionable biomarkers and the expansion of treatment options, thereby prolonging cancer patient survival. Case Presentation: We herein present the case of a female 54-year-old patient diagnosed with melanoma of the right knee, for which she underwent surgery. Patient showed progression of disease after 10 cycles of adjuvant nivolumab. Ipilimumab (1 mg/kg every 3 weeks) was added to the treatment regimen but no clinical improvement was observed. Molecular profiling was conducted based on patient tissue, and an ANXA2-NTRK3 fusion was detected in the tumor. This specific fusion has not been previously reported; however, it is in-frame and similar to other known oncogenic NTRK fusions. At the time of entrectinib initiation, the patient had clear disease progression on the right leg on standard of care immunotherapy. She was commenced on entrectinib 200 mg once daily for 2 weeks. Dose escalation was attempted, and treatment intensity was managed based on drug tolerability. Good treatment response was observed on laboratory and radiologic parameters. As of September 2023, i.e., 2.5 years after treatment initiation, patient disease continues to be controlled with entrectinib. Conclusion: Profiling of advanced tumors is important to determine the presence of agnostic markers that can be targeted and ultimately improve the prognostic outcome of patients after the failure of standard of care.

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Annexins and cardiovascular diseases: Beyond membrane trafficking and repair

Cited by 13 publications

References 163 publications

Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

Left ventricular remodeling in normotensive Wistar rats exposed to intermittent hypoxia of different duration

Entrectinib for NTRK Fusion-Positive Metastatic Melanoma Progressing on Combined PD-1 and CTLA-4 Inhibition: A Case Report

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