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Article ; Online: Regulation of cardiac fibroblasts by lymphocytes after a myocardial infarction: playing in the major league.

Learmonth, Maya / Corker, Alexa / Dasgupta, Shaoni / DeLeon-Pennell, Kristine Y

American journal of physiology. Heart and circulatory physiology

2023 Volume 325, Issue 3, Page(s) H553–H561

Abstract: Cardiac fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix components within the myocardium, which can lead to impaired cardiac function and heart failure. Studies have shown that lymphocytes including B ... ...

Abstract	Cardiac fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix components within the myocardium, which can lead to impaired cardiac function and heart failure. Studies have shown that lymphocytes including B and T cells play important roles in the development and progression of cardiac fibrosis after a myocardial infarction. In this review, we focus on the regulation of cardiac fibrosis by lymphocyte subsets, with a particular emphasis on CD4
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes ; Myocardial Infarction/pathology ; Myocardium/pathology ; Fibroblasts/pathology ; Cardiomyopathies/pathology ; Heart Failure/pathology ; Fibrosis ; Ventricular Remodeling
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00250.2023
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Article ; Online: Cardiac and vascular complications in lupus: Is there a role for sex?

Corker, Alexa / Learmonth, Maya / Patrick, David M / DeLeon-Pennell, Kristine Y / Van Beusecum, Justin P

Frontiers in immunology

2023 Volume 14, Page(s) 1098383

Abstract: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disorder and is characterized by autoantibody formation and subsequent immune complex deposition into target organs. SLE affects nearly nine women to every one man worldwide. Patients ... ...

Abstract	Systemic lupus erythematosus (SLE) is a common systemic autoimmune disorder and is characterized by autoantibody formation and subsequent immune complex deposition into target organs. SLE affects nearly nine women to every one man worldwide. Patients with SLE are at an enhanced risk for cardiovascular disease (CVD) morbidity and mortality. CVD is the leading cause of death worldwide and includes heart and blood vessel disorders, cerebrovascular disease, and rheumatic heart disease. Specific mechanisms by which cardiac and vascular pathophysiology develops in patients with SLE are still not fully known. Not only do we not understand this correlation between SLE and CVD, but there is also a critical gap in scientific knowledge on the contribution of sex. In this review, we will discuss the cardiac and vascular pathological disease states that are present in some patients with SLE. More importantly, we will discuss the potential mechanisms for the role of sex and sex hormones in the development of CVD with SLE.
MeSH term(s)	Male ; Humans ; Female ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/complications ; Lupus Erythematosus, Systemic ; Autoantibodies ; Disease Progression
Chemical Substances	Autoantibodies
Language	English
Publishing date	2023-03-29
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1098383
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Article ; Online: Organized Chaos: Deciphering Immune Cell Heterogeneity's Role in Inflammation in the Heart.

Corker, Alexa / Neff, Lily S / Broughton, Philip / Bradshaw, Amy D / DeLeon-Pennell, Kristine Y

Biomolecules

2021 Volume 12, Issue 1

Abstract: During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. ...

Abstract	During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. In response to injury, there is an increase in inflammation within the heart due to the influx of immune cells. Some of the most common immune cells recruited to the heart are macrophages, dendritic cells, neutrophils, and T-cells. In this review, we will discuss what is known about cardiac immune cell heterogeneity during homeostasis, how these cell populations change in response to a pathology such as myocardial infarction or pressure overload, and what stimuli are regulating these processes. In addition, we will summarize technologies used to evaluate cell heterogeneity in models of cardiovascular disease.
MeSH term(s)	Animals ; Humans ; Inflammation/immunology ; Macrophages/immunology ; Models, Cardiovascular ; Myocardial Infarction/immunology ; Myocardium/immunology
Language	English
Publishing date	2021-12-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12010011
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Article ; Online: Riding the wave: a quantitative report of electrocardiogram utilization for myocardial infarction confirmation.

Broughton, Philip / Troncoso, Miguel / Corker, Alexa / Williams, Alexus / Bolus, Dawson / Munoz, Gualberto / McWhorter, Caroline / Roerden, Hallie / Huebsch, Penny / DeLeon-Pennell, Kristine Y

American journal of physiology. Heart and circulatory physiology

2022 Volume 323, Issue 3, Page(s) H378–H387

Abstract: The purpose of this study was to generate a quantitative profile of electrocardiograms (ECGs) for confirming surgical success of permanent coronary artery ligation. An ECG was recorded at baseline, and 0, 1, and 5 min after ligation and analyzed using ... ...

Abstract	The purpose of this study was to generate a quantitative profile of electrocardiograms (ECGs) for confirming surgical success of permanent coronary artery ligation. An ECG was recorded at baseline, and 0, 1, and 5 min after ligation and analyzed using iWorkx LabScribe software.
MeSH term(s)	Animals ; Electrocardiography ; Female ; Humans ; Male ; Mice ; Myocardial Infarction/diagnosis ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity
Language	English
Publishing date	2022-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00201.2022
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Article ; Online: Elevated Neutrophil Gelatinase-Associated Lipocalin Is Associated With the Severity of Kidney Injury and Poor Prognosis of Patients With COVID-19.

Xu, Katherine / Shang, Ning / Levitman, Abraham / Corker, Alexa / Kudose, Satoru / Yaeh, Andrew / Neupane, Uddhav / Stevens, Jacob / Sampogna, Rosemary / Mills, Angela M / D'Agati, Vivette / Mohan, Sumit / Kiryluk, Krzysztof / Barasch, Jonathan

Kidney international reports

2021 Volume 6, Issue 12, Page(s) 2979–2992

Abstract: Introduction: Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission ... ...

Abstract	Introduction: Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with acute kidney injury (AKI) in those with COVID-19 infection. Methods: This is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores. Results: Admission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, Conclusion: In the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.
Language	English
Publishing date	2021-10-08
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2021.09.005
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Article ; Online: Chronic

Zaidi, Yusra / Corker, Alexa / Vasileva, Valeriia Y / Oviedo, Kimberly / Graham, Connor / Wilson, Kyrie / Martino, John / Troncoso, Miguel / Broughton, Philip / Ilatovskaya, Daria V / Lindsey, Merry L / DeLeon-Pennell, Kristine Y

American journal of physiology. Heart and circulatory physiology

2021 Volume 321, Issue 5, Page(s) H948–H962

Abstract: Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study ... ...

Abstract	Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS,
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cells, Cultured ; Disease Models, Animal ; Female ; Immunologic Memory ; Inflammation Mediators/metabolism ; Lipopolysaccharides ; Lymphocyte Activation ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Mice ; Myocardial Infarction/immunology ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardium/immunology ; Myocardium/metabolism ; Myocardium/pathology ; Periodontitis/chemically induced ; Periodontitis/immunology ; Periodontitis/metabolism ; Periodontitis/pathology ; Phagocytosis ; Phenotype ; Porphyromonas gingivalis ; Time Factors ; Wound Healing
Chemical Substances	Inflammation Mediators ; Lipopolysaccharides
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00082.2021
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Article ; Online: Antimicrobial-induced oral dysbiosis exacerbates naturally occurring alveolar bone loss.

Swanson, Brooks A / Carson, Matthew D / Hathaway-Schrader, Jessica D / Warner, Amy J / Kirkpatrick, Joy E / Corker, Alexa / Alekseyenko, Alexander V / Westwater, Caroline / Aguirre, J Ignacio / Novince, Chad M

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 11, Page(s) e22015

Abstract: Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal ... ...

Abstract	Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased T
MeSH term(s)	Alveolar Bone Loss/microbiology ; Animals ; Anti-Bacterial Agents/adverse effects ; Dysbiosis/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Host Microbial Interactions ; Male ; Mice ; Mice, Inbred C57BL
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202101169R
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Article ; Online: Urine test predicts kidney injury and death in COVID-19

Xu, Katherine / Shang, Ning / Levitman, Abraham / Corker, Alexa / Kudose, Satoru / Yaeh, Andrew / Neupane, Uddhav / Stevens, Jacob / Mohan, Sumit / Sampogna, Rosemary / D'Agati, Vivette / Kiryluk, Krzysztof / Barasch, Jonathan

medRxiv

Abstract: ... Background: ... Kidney injury is common in COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We hypothesized that molecular markers of tubular injury could diagnose COVID-19 associated kidney damage ...

Abstract	Background: Kidney injury is common in COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We hypothesized that molecular markers of tubular injury could diagnose COVID-19 associated kidney damage and predict its clinical course. Methods: This is a prospective cohort study of 444 consecutive COVID-19 patients (43.9% females, 20.5% African American, 54.1% Latinx) in Columbia University9s Emergency Department at the peak of the New York pandemic (March-April 2020). Urine and blood were collected simultaneously at admission (median time of day 0, IQR 0-2 days) and within 1 day of a positive SARS-CoV-2 test in 70% of patients. Biomarker assays were blinded to clinical data. Results: Urinary NGAL (uNGAL) was strongly associated with AKI diagnosis (267±301 vs. 96±139 ng/mL, P=1.6x10<sup>-10</sup>). uNGAL >150ng/mL had 80% specificity and 75% sensitivity to diagnose AKIN stage 2 or higher. uNGAL quantitatively predicted the duration of AKI and outcomes, including death, dialysis, shock, and longer hospital stay. The risk of death increased 73% per standard deviation of uNGAL [OR (95%CI): 1.73 (1.29-2.33), P=2.8x10<sup>-4</sup>] and was independent of baseline SCr, co-morbidities, and proteinuria [adjusted OR (95%CI): 1.51 (1.10-2.11), P=1.2x10<sup>-2</sup>]. Proteinuria and uKIM-1 also indicated tubular injury, but were not diagnostic of AKI. Typically, distal nephron segments transcribe NGAL, but in COVID-19 biopsies with widespread acute tubular injury (ATI), NGAL expression overlapped KIM-1 in proximal tubules. Conclusion: uNGAL predicted the diagnosis, duration, and severity of AKI and ATI, as well as hospital stay, dialysis, shock, and death in patients with acute COVID-19.
Keywords	covid19
Language	English
Publishing date	2021-06-14
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.06.10.21258638
Database	COVID19

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Article ; Online: Rule Out Acute Kidney Injury in the Emergency Department With a Urinary Dipstick.

Stevens, Jacob S / Xu, Katherine / Corker, Alexa / Gopal, Tejashree S / Sayan, Osman R / Geraghty, Erin P / Yaeh, Andrew M / Kosuri, Yaagnik D / Burton, John R / Lincoln, Saul V / Callahan, Miriam P / Breheney, Rebecca K / Beenken, Andrew S / Gamino, Juliana N / Felman, Ariel E / Gehani, Anjali / Giordano, Hayley A / Gozali, Aileen / Guerrero Herrera, Eddie F /

Hatcher, Britney A / Kheir, Lena A / Li, Yuanji / Mitsui, Erika K / Nha, Jae I / Sayan, Alexander T / Spaiser, Samuel J / Arumugam, Siddarth / Sia, Samuel K / King, Kristen L / Mohan, Sumit / Barasch, Jonathan

Kidney international reports

2020 Volume 5, Issue 11, Page(s) 1982–1992

Abstract: Introduction: The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of ... ...

Abstract	Introduction: The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time. Methods: To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort Results: Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (ρ = 0.732, Conclusion: We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr.
Language	English
Publishing date	2020-09-18
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2020.09.006
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