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  1. Article: Upregulation of Endothelin-1 May Predict Chemotherapy-Induced Cardiotoxicity in Women with Breast Cancer.

    Krishnarao, Krithika / Bruno, Katelyn A / Di Florio, Damian N / Edenfield, Brandy H / Whelan, Emily R / Macomb, Logan P / McGuire, Molly M / Hill, Anneliese R / Ray, Jordan C / Cornell, Lauren F / Tan, Winston / Geiger, Xochiquetzal J / Salomon, Gary R / Douglass, Erika J / Fairweather, DeLisa / Yamani, Mohamad H

    Journal of clinical medicine

    2022  Volume 11, Issue 12

    Abstract: As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving ... ...

    Abstract As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (
    Language English
    Publishing date 2022-06-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm11123547
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Trpc6 Promotes Doxorubicin-Induced Cardiomyopathy in Male Mice With Pleiotropic Differences Between Males and Females.

    Norton, Nadine / Bruno, Katelyn A / Di Florio, Damian N / Whelan, Emily R / Hill, Anneliese R / Morales-Lara, Andrea Carolina / Mease, Anna A / Sousou, John M / Malavet, Jose A / Dorn, Lauren E / Salomon, Gary R / Macomb, Logan P / Khatib, Sami / Anastasiadis, Zacharias P / Necela, Brian M / McGuire, Molly M / Giresi, Presley G / Kotha, Archana / Beetler, Danielle J /
    Weil, Raegan M / Landolfo, Carolyn K / Fairweather, DeLisa

    Frontiers in cardiovascular medicine

    2022  Volume 8, Page(s) 757784

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-01-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2021.757784
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice.

    Beetler, Danielle J / Bruno, Katelyn A / Watkins, Molly M / Xu, Vivian / Chekuri, Isha / Giresi, Presley / Di Florio, Damian N / Whelan, Emily R / Edenfield, Brandy H / Walker, Sierra A / Morales-Lara, Andrea C / Hill, Anneliese R / Jain, Angita / Auda, Matthew E / Macomb, Logan P / Shapiro, Kathryn A / Keegan, Kevin C / Wolfram, Joy / Behfar, Atta /
    Stalboerger, Paul G / Terzic, Andre / Farres, Houssam / Cooper, Leslie T / Fairweather, DeLisa

    Small (Weinheim an der Bergstrasse, Germany)

    2023  Volume 19, Issue 49, Page(s) e2303317

    Abstract: Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular ... ...

    Abstract Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human-platelet-derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll-like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL-1β), transforming growth factor-beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7-9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T-cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.
    MeSH term(s) Humans ; Mice ; Male ; Female ; Animals ; Myocarditis ; Myocardium/metabolism ; Cardiomyopathy, Dilated/metabolism ; Immunity, Innate ; Macrophages/metabolism
    Language English
    Publishing date 2023-08-23
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.202303317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Association of Genetic Variants at

    Norton, Nadine / Crook, Julia E / Wang, Liwei / Olson, Janet E / Kachergus, Jennifer M / Serie, Daniel J / Necela, Brian M / Borgman, Paul G / Advani, Pooja P / Ray, Jordan C / Landolfo, Carolyn / Di Florio, Damian N / Hill, Anneliese R / Bruno, Katelyn A / Fairweather, DeLisa

    Frontiers in cardiovascular medicine

    2020  Volume 7, Page(s) 142

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-08-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2020.00142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis.

    Bruno, Katelyn A / Macomb, Logan P / Morales-Lara, A Carolina / Mathews, Jessica E / Frisancho, J Augusto / Yang, Alex L / Di Florio, Damian N / Edenfield, Brandy H / Whelan, Emily R / Salomon, Gary R / Hill, Anneliese R / Hewa-Rahinduwage, Chathuranga C / Scott, Ashley J / Greyner, Henry D / Molina, Frank A / Greenaway, Merci S / Cooper, George M / Fairweather, DeLisa

    International journal of molecular sciences

    2021  Volume 22, Issue 16

    Abstract: Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized ... ...

    Abstract Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers.
    Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection.
    Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis.
    Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.
    MeSH term(s) Animals ; Coxsackievirus Infections/complications ; Coxsackievirus Infections/virology ; Enterovirus B, Human/pathogenicity ; Female ; Housing, Animal/statistics & numerical data ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis/etiology ; Myocarditis/pathology ; Myocarditis/virology ; Plastics/adverse effects ; Sex Factors
    Chemical Substances Plastics
    Language English
    Publishing date 2021-08-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22168834
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Elevated Sera sST2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis.

    Coronado, Michael J / Bruno, Katelyn A / Blauwet, Lori A / Tschöpe, Carsten / Cunningham, Madeleine W / Pankuweit, Sabine / van Linthout, Sophie / Jeon, Eun-Seok / McNamara, Dennis M / Krejčí, Jan / Bienertová-Vašků, Julie / Douglass, Erika J / Abston, Eric D / Bucek, Adriana / Frisancho, J Augusto / Greenaway, Merci S / Hill, Anneliese R / Schultheiss, Heinz-Peter / Cooper, Leslie T /
    Fairweather, DeLisa

    Journal of the American Heart Association

    2019  Volume 8, Issue 2, Page(s) e008968

    Abstract: Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera ... ...

    Abstract Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST2 levels were higher in healthy men ( P=8×10
    MeSH term(s) Adult ; Age Factors ; Animals ; Biomarkers/blood ; Biopsy ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Heart Failure/blood ; Heart Failure/diagnosis ; Heart Failure/etiology ; Humans ; Interleukin-1 Receptor-Like 1 Protein/blood ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Myocarditis/blood ; Myocarditis/complications ; Myocarditis/diagnosis ; Myocardium/pathology ; Prognosis ; Retrospective Studies ; Sex Factors
    Chemical Substances Biomarkers ; IL1RL1 protein, human ; Interleukin-1 Receptor-Like 1 Protein
    Language English
    Publishing date 2019-01-13
    Publishing country England
    Document type Comparative Study ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.118.008968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation.

    Fiesel, Fabienne C / Ando, Maya / Hudec, Roman / Hill, Anneliese R / Castanedes-Casey, Monica / Caulfield, Thomas R / Moussaud-Lamodière, Elisabeth L / Stankowski, Jeannette N / Bauer, Peter O / Lorenzo-Betancor, Oswaldo / Ferrer, Isidre / Arbelo, José M / Siuda, Joanna / Chen, Li / Dawson, Valina L / Dawson, Ted M / Wszolek, Zbigniew K / Ross, Owen A / Dickson, Dennis W /
    Springer, Wolfdieter

    EMBO reports

    2015  Volume 16, Issue 9, Page(s) 1114–1130

    Abstract: Mutations in PINK1 and PARKIN cause recessive, early-onset Parkinson's disease (PD). Together, these two proteins orchestrate a protective mitophagic response that ensures the safe disposal of damaged mitochondria. The kinase PINK1 phosphorylates ... ...

    Abstract Mutations in PINK1 and PARKIN cause recessive, early-onset Parkinson's disease (PD). Together, these two proteins orchestrate a protective mitophagic response that ensures the safe disposal of damaged mitochondria. The kinase PINK1 phosphorylates ubiquitin (Ub) at the conserved residue S65, in addition to modifying the E3 ubiquitin ligase Parkin. The structural and functional consequences of Ub phosphorylation (pS65-Ub) have already been suggested from in vitro experiments, but its (patho-)physiological significance remains unknown. We have generated novel antibodies and assessed pS65-Ub signals in vitro and in cells, including primary neurons, under endogenous conditions. pS65-Ub is dependent on PINK1 kinase activity as confirmed in patient fibroblasts and postmortem brain samples harboring pathogenic mutations. We show that pS65-Ub is reversible and barely detectable under basal conditions, but rapidly induced upon mitochondrial stress in cells and amplified in the presence of functional Parkin. pS65-Ub accumulates in human brain during aging and disease in the form of cytoplasmic granules that partially overlap with mitochondrial, lysosomal, and total Ub markers. Additional studies are now warranted to further elucidate pS65-Ub functions and fully explore its potential for biomarker or therapeutic development.
    MeSH term(s) Animals ; Antibodies ; Biomarkers ; Brain/cytology ; Fibroblasts ; HeLa Cells ; Humans ; Mice ; Mitochondria/physiology ; Mitophagy/genetics ; Mutation ; Neurons/metabolism ; Neurons/ultrastructure ; Parkinson Disease/genetics ; Parkinson Disease/physiopathology ; Phosphorylation ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Ubiquitin/genetics ; Ubiquitin/immunology ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Chemical Substances Antibodies ; Biomarkers ; Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-) ; PTEN-induced putative kinase (EC 2.7.11.1)
    Language English
    Publishing date 2015-07-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201540514
    Database MEDical Literature Analysis and Retrieval System OnLINE

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