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Article ; Online: The chicken, the egg, and the elephant: eNOS and NRG1 in fibrosis.

Nishat, Shamama / Gumina, Richard J

American journal of physiology. Heart and circulatory physiology

2021 Volume 321, Issue 2, Page(s) H292–H293

MeSH term(s)	Animals ; Fibrosis ; Humans ; Neuregulin-1 ; Nitric Oxide Synthase Type III
Chemical Substances	NRG1 protein, human ; Neuregulin-1 ; NOS3 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39)
Language	English
Publishing date	2021-06-25
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00308.2021
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Article ; Online: Immune cell Dilemma in Ischemic Cardiomyopathy: To Heal or Not to Heal.

Nehra, Sarita / Gumina, Richard J / Bansal, Shyam S

Current opinion in physiology

2020 Volume 19, Page(s) 39–46

Abstract: Inflammation is a double-edged sword for sterile tissue injury such as in myocardial infarction (MI). After ischemic injury, inflammatory immune responses activate repair processes, clear tissue-debris, form a stable scar and initiate angiogenesis in the ...

Abstract	Inflammation is a double-edged sword for sterile tissue injury such as in myocardial infarction (MI). After ischemic injury, inflammatory immune responses activate repair processes, clear tissue-debris, form a stable scar and initiate angiogenesis in the myocardium for efficient wound-healing. However, incomplete immune resolution or sustained low-grade inflammation lead to ischemic cardiomyopathy (IC) characterized by maladaptive tissue remodeling and left-ventricular dilatation. It is clear that a delicate balance of cytokines, chemokines, prostaglandins, resolvins, and the innate and adaptive immune systems is critical for adequate healing as both insufficient- or overt-activation of inflammatory responses can either enhance rupture incidence or exacerbate cardiac dysfunction in the long-term. Among all the players, immune cells are the most critical as they are not only a source for all of the inflammatory protein mediators, but are also a target. However, phenotypic complexities associated with different immune subtypes, their interdependence, phasic-activations and varied functionalities often make it difficult to segregate the effects of one immune cell from another. In this review, we briefly summarize the role of several innate and adaptive immune cells to acquaint readers with complex immune-networks that dictate the extent of wound-healing post-MI and maladaptive remodeling during IC.
Language	English
Publishing date	2020-09-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2918626-2
ISSN	2468-8673 ; 2468-8681
ISSN (online)	2468-8673
ISSN	2468-8681
DOI	10.1016/j.cophys.2020.09.002
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Article: The role of CD38 in ischemia reperfusion injury in cardiopulmonary bypass and thoracic transplantation: a narrative review.

Gouchoe, Doug A / Vijayakumar, Ammu / Aly, Ahmed H / Cui, Ervin Y / Essandoh, Michael / Gumina, Richard J / Black, Sylvester M / Whitson, Bryan A

Journal of thoracic disease

2023 Volume 15, Issue 10, Page(s) 5736–5749

Abstract: Background and objective: Ischemia reperfusion injury (IRI) is often the underlying cause of endothelium breakdown and damage in cardiac or transplantation operations, which can lead to disastrous post-operative consequences. Recent studies of cluster ... ...

Abstract	Background and objective: Ischemia reperfusion injury (IRI) is often the underlying cause of endothelium breakdown and damage in cardiac or transplantation operations, which can lead to disastrous post-operative consequences. Recent studies of cluster of differentiation 38 (CD38) have identified its critical role in IRI. Our objective is to provide a comprehensive overview of CD38-mediated axis, pathways, and potential CD38 translational therapies for reducing inflammation associated with cardiopulmonary bypass (CPB) or thoracic transplantation and IRI. Methods: We conducted a review of the literature by performing a search of the PubMed database on 2 April 2023. To find relevant publications on CD38, we utilized the MeSH terms: "CD38" AND "Ischemia" OR "CD38" AND "Transplant" OR "CD38" AND "Heart" from 1990-2023. Additional papers were included if they were felt to be relevant but were not captured in the MeSH terms. We found 160 papers that met this criterion, and following screening, exclusion and consensus a total of 36 papers were included. Key content and findings: CD38 is most notably a nicotine adenine dinucleotide (NAD) Conclusions: The knowledge gap in understanding the molecular basis of IRI has prevented further development of novel therapies and treatments. The possible interaction of CD38 with CD39 in the endothelium, and the modulation of the CD38 axis may be a pathway to improve cardiovascular outcomes, heart and lung donor organ quality, and overall longevity.
Language	English
Publishing date	2023-09-11
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-23-725
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Article ; Online: Estrogenic bias in T-Lymphocyte biology: Implications for cardiovascular disease.

Rosenzweig, Rachel / Gupta, Sahil / Kumar, Vinay / Gumina, Richard J / Bansal, Shyam S

Pharmacological research

2021 Volume 170, Page(s) 105606

Abstract: Gender bias in cardiovascular disease has been extensively documented in epidemiological and clinical studies. Despite this, the precise molecular mechanisms underlying these disparities between men and women are poorly understood. It is clear that ... ...

Abstract	Gender bias in cardiovascular disease has been extensively documented in epidemiological and clinical studies. Despite this, the precise molecular mechanisms underlying these disparities between men and women are poorly understood. It is clear that physiological concentrations of estradiol, such as those present in pre-menopausal women, exert cardioprotective effects that are absent in men or in post-menopausal women. These cardioprotective effects, in part, are due to the estrogen receptor-mediated modulation of the immune system including T-cells. Estrogen receptors (ERs) are widely expressed in different T-cell subsets which are known to play an indispensable role in the progression of cardiovascular disease. Because T-cells can be polarized into several distinct subsets depending on the activation milieu, they can have many different, potentially opposing functions, and it is unclear what roles estrogen receptor signaling may play in mediating these functions. This is further complicated by the discrete and often antagonistic actions of different ERs on T-cell biology which dictate the balance between numerous ER-dependent signaling pathways. While myriad effects of estrogen in T-cells are relevant for many cardiovascular diseases, their widespread effects on several other (patho)physiological systems introduce several obstacles to understanding ER signaling and its precise effects on the immune system. This review aims to provide a more comprehensive summary of the mechanisms of estrogen receptor-mediated modulation of T-cell function, polarization, and cytokine production in the context of cardiovascular disease.
MeSH term(s)	Animals ; Cardiovascular Diseases/immunology ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/physiopathology ; Cardiovascular System/immunology ; Cardiovascular System/metabolism ; Cardiovascular System/physiopathology ; Cytokines/metabolism ; Estradiol/metabolism ; Female ; Humans ; Ligands ; Lymphocyte Activation ; Male ; Phenotype ; Receptors, Estrogen/metabolism ; Sex Characteristics ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Cytokines ; Ligands ; Receptors, Estrogen ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2021-06-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105606
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Article: Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art.

Al-Abcha, Abdullah / Radwan, Yasser / Blais, Danielle / Mazzaferri, Ernest L / Boudoulas, Konstantinos Dean / Essa, Essa M / Gumina, Richard J

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 850028

Abstract: The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to ... ...

Abstract	The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of "antiplatelet" therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.850028
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Article ; Online: Estrogen Receptor-β Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling During Chronic Heart Failure.

Rosenzweig, Rachel / Kumar, Vinay / Gupta, Sahil / Bermeo-Blanco, Oscar / Stratton, Matthew S / Gumina, Richard J / Bansal, Shyam S

Circulation. Heart failure

2022 Volume 15, Issue 7, Page(s) e008997

Abstract: Background: CD4: Methods: RNA-sequencing of cardiac CD4: Results: RNA-sequencing of CD4: Conclusions: Our studies indicate that ERβ agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit ... ...

Abstract	Background: CD4 Methods: RNA-sequencing of cardiac CD4 Results: RNA-sequencing of CD4 Conclusions: Our studies indicate that ERβ agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit CD4
MeSH term(s)	Animals ; Chronic Disease ; Estrogen Receptor alpha ; Estrogen Receptor beta/physiology ; Estrogen Receptor beta/therapeutic use ; Estrogens/therapeutic use ; Female ; Heart Failure ; Lymphocyte Activation ; Male ; Mice ; Myocardial Infarction/metabolism ; RNA/therapeutic use ; Receptors, Estrogen/therapeutic use ; Ventricular Remodeling/physiology
Chemical Substances	Estrogen Receptor alpha ; Estrogen Receptor beta ; Estrogens ; Receptors, Estrogen ; RNA (63231-63-0)
Language	English
Publishing date	2022-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2429459-7
ISSN	1941-3297 ; 1941-3289
ISSN (online)	1941-3297
ISSN	1941-3289
DOI	10.1161/CIRCHEARTFAILURE.121.008997
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Zs.A 6745: Show issues

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Article ; Online: E-Cigarettes and Cardiopulmonary Health: Review for Clinicians.

Neczypor, Evan W / Mears, Matthew J / Ghosh, Arunava / Sassano, M Flori / Gumina, Richard J / Wold, Loren E / Tarran, Robert

Circulation

2022 Volume 145, Issue 3, Page(s) 219–232

Abstract: Electronic cigarettes (e-cigarettes) are battery powered electronic nicotine delivery systems that use a propylene glycol/vegetable glycerin base to deliver vaporized nicotine and flavorings to the body. E-cigarettes became commercially available without ...

Abstract	Electronic cigarettes (e-cigarettes) are battery powered electronic nicotine delivery systems that use a propylene glycol/vegetable glycerin base to deliver vaporized nicotine and flavorings to the body. E-cigarettes became commercially available without evidence regarding their risks, long-term safety, or utility in smoking cessation. Recent clinical trials suggest that e-cigarette use with counseling may be effective in reducing cigarette use but not nicotine dependence. However, meta-analyses of observational studies demonstrate that e-cigarette use is not associated with smoking cessation. Cardiovascular studies reported sympathetic activation, vascular stiffening, and endothelial dysfunction, which are associated with adverse cardiovascular events. The majority of pulmonary clinical trials in e-cigarette users included standard spirometry as the primary outcome measure, reporting no change in lung function. However, studies reported increased biomarkers of pulmonary disease in e-cigarette users. These studies were conducted in adults, but >30% of high school-age adolescents reported e-cigarette use. The effects of e-cigarette use on cardiopulmonary endpoints in adolescents and young adults remain unstudied. Because of adverse clinical findings and associations between e-cigarette use and increased incidence of respiratory diseases in people who have never smoked, large longitudinal studies are needed to understand the risk profile of e-cigarettes. Consistent with the Centers for Disease Control and Prevention recommendations, clinicians should monitor the health risks of e-cigarette use, discourage nonsmokers and adolescents from using e-cigarettes, and discourage smokers from engaging in dual use without cigarette reduction or cessation.
MeSH term(s)	Cigarette Smoking/adverse effects ; Electronic Nicotine Delivery Systems ; Humans ; Physician's Role ; Smoking/epidemiology ; Tobacco Use Disorder/prevention & control ; Vaping/adverse effects
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.121.056777
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Article ; Online: Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection.

Evans, John P / Zeng, Cong / Carlin, Claire / Lozanski, Gerard / Saif, Linda J / Oltz, Eugene M / Gumina, Richard J / Liu, Shan-Lu

Science translational medicine

2022 Volume 14, Issue 637, Page(s) eabn8057

Abstract: The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody ... ...

Abstract	The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody response against the spike protein of five major SARS-CoV-2 variants, D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in health care workers (HCWs) vaccinated with SARS-CoV-2 mRNA vaccines. Serum samples were collected before vaccination, 3 weeks after first vaccination, 1 month after second vaccination, and 6 months after second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for most patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein-bearing pseudoviruses declined markedly from 1 to 6 months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. In addition, mRNA-1273-vaccinated HCWs exhibited about twofold higher neutralizing antibody titers than BNT162b2-vaccinated HCWs. Together, these results demonstrate possible waning of antibody-mediated protection against SARS-CoV-2 variants that is dependent on prior infection status and the mRNA vaccine received. They also show that the Omicron variant spike protein can almost completely escape from neutralizing antibodies elicited in recipients of only two mRNA vaccine doses.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; RNA, Messenger/genetics ; SARS-CoV-2 ; Vaccination ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Synthetic ; mRNA Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abn8057
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Article ; Online: Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants.

Qu, Panke / Xu, Kai / Faraone, Julia N / Goodarzi, Negin / Zheng, Yi-Min / Carlin, Claire / Bednash, Joseph S / Horowitz, Jeffrey C / Mallampalli, Rama K / Saif, Linda J / Oltz, Eugene M / Jones, Daniel / Gumina, Richard J / Liu, Shan-Lu

Cell

2024 Volume 187, Issue 3, Page(s) 585–595.e6

Abstract: Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose- ... ...

Abstract	Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially different conformational stability of BA.2.86 spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
MeSH term(s)	Humans ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/immunology ; COVID-19 Vaccines ; Immune Evasion ; SARS-CoV-2/classification ; SARS-CoV-2/physiology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.12.026
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Article: Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion.

Li, Pei / Liu, Yajie / Faraone, Julia / Hsu, Cheng Chih / Chamblee, Michelle / Zheng, Yi-Min / Carlin, Claire / Bednash, Joseph S / Horowitz, Jeffrey C / Mallampalli, Rama K / Saif, Linda J / Oltz, Eugene M / Jones, Daniel / Li, Jianrong / Gumina, Richard J / Liu, Shan-Lu

bioRxiv : the preprint server for biology

2024

Abstract: The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization ... ...

Abstract	The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.11.583978
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