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Article ; Online: Finding Needles in the Gut Microbiota's Haystack.

Aljadah, Michael / Widlansky, Michael E

2023 Volume 132, Issue 2, Page(s) 182–184

MeSH term(s)	Gastrointestinal Microbiome ; Needles ; Microbiota
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.122.322354
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Article ; Online: Proteomic Profiles of Human Arterioles Isolated From Fresh Adipose Tissue or Following Overnight Storage.

Pandey, Rajan / Roberts, Michelle L / Wang, Jingli / Pereckas, Michaela / Jensen, David / Greene, Andrew S / Widlansky, Michael E / Liang, Mingyu

Laboratory investigation; a journal of technical methods and pathology

2024 Volume 104, Issue 5, Page(s) 102036

Abstract: Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 μg, making ... ...

Abstract	Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 μg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility, especially for powerful multicenter clinical studies in which clinical specimens need to be shipped overnight to a research laboratory for arteriole isolation. We performed a study to address low-input, test overnight tissue storage and develop a reference human arteriolar proteomic profile. In tandem mass tag proteomics, use of a booster channel consisting of human induced pluripotent stem cell-derived endothelial and vascular smooth muscle cells (1:5 ratio) increased the number of proteins detected in a human arteriole segment with a false discovery rate of <0.01 from 1051 to more than 3000. The correlation coefficient of proteomic profile was similar between replicate arterioles isolated freshly, following cold storage, or before and after the cold storage (1-way analysis of variance; P = .60). We built a human arteriolar proteomic profile consisting of 3832 proteins based on the analysis of 12 arteriole samples from 3 subjects. Of 1945 blood pressure-relevant proteins that we curated, 476 (12.5%) were detected in the arteriolar proteome, which was a significant overrepresentation (χ
Language	English
Publishing date	2024-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1016/j.labinv.2024.102036
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Article ; Online: Mitochondrial regulation of diabetic vascular disease: an emerging opportunity.

Widlansky, Michael E / Hill, R Blake

Translational research : the journal of laboratory and clinical medicine

2018 Volume 202, Page(s) 83–98

Abstract: Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and ... ...

Abstract	Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and clinicians to collaborate on targeting mechanisms and pathways that specifically contribute to vascular pathology in patients with diabetes mellitus. Dysfunctional mitochondria producing excessive mitochondrial reactive oxygen species (mtROS) play a proximal cell-signaling role in the development of vascular endothelial dysfunction in the setting of diabetes. Targeting the mechanisms of production of mtROS or mtROS themselves represents an attractive method to reduce the prevalence and severity of diabetic vascular disease. This review focuses on the role of mitochondria in the development of diabetic vascular disease and current developments in methods to improve mitochondrial health to improve vascular outcomes in patients with DM.
MeSH term(s)	Animals ; Diabetic Angiopathies/metabolism ; Diabetic Angiopathies/pathology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Humans ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Mitophagy ; Reactive Oxygen Species/metabolism
Chemical Substances	Mitochondrial Proteins ; Reactive Oxygen Species
Language	English
Publishing date	2018-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2018.07.015
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Article ; Online: 17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.

SenthilKumar, Gopika / Katunaric, Boran / Bordas-Murphy, Henry / Young, Micaela / Doren, Erin L / Schulz, Mary E / Widlansky, Michael E / Freed, Julie K

American journal of physiology. Heart and circulatory physiology

2023 Volume 324, Issue 3, Page(s) H330–H337

Abstract: Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender- ... ...

Abstract	Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females' risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited. Here, we show that isolated human arterioles from females across the life span maintain nitric oxide (NO)-mediated dilation to flow, whereas chronic (16-20 h) exposure to exogenous (100 nM) 17β-estradiol promotes microvascular endothelial dysfunction in vessels from adult females of <40 and ≥40 yr of age. The damaging effect of estrogen was more dramatic in arterioles from biological males, as they exhibited both endothelial and smooth muscle dysfunction. Furthermore, females of <40 yr have greater endothelial expression of estrogen receptor-β (ER-β) and G protein-coupled estrogen receptor (GPER) compared with females of ≥40 yr and males. Estrogen receptor-α (ER-α), the prominent receptor associated with protective effects of estrogen, was identified within the adventitia as opposed to the endothelium across all groups. To our knowledge, this is the first study to report the detrimental effects of estrogen on the human microvasculature and highlights differences in estrogen receptor expression.
MeSH term(s)	Male ; Adult ; Female ; Humans ; Arterioles/metabolism ; Receptors, Estrogen/metabolism ; Vasodilation ; Estradiol/pharmacology ; Estradiol/metabolism ; Estrogens/pharmacology ; Estrogens/metabolism ; Vascular Diseases/metabolism ; Estrogen Receptor alpha/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Endothelium, Vascular/metabolism
Chemical Substances	Receptors, Estrogen ; Estradiol (4TI98Z838E) ; Estrogens ; Estrogen Receptor alpha ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2023-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00708.2022
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Article ; Online: Role of the circulating milieu in age-related arterial dysfunction: a novel ex vivo approach.

Mahoney, Sophia A / VanDongen, Nicholas S / Greenberg, Nathan T / Venkatasubramanian, Ravinandan / Rossman, Matthew J / Widlansky, Michael E / Brunt, Vienna E / Bernaldo de Quirós, Yara / Seals, Douglas R / Clayton, Zachary S

American journal of physiology. Heart and circulatory physiology

2024 Volume 326, Issue 5, Page(s) H1279–H1290

Abstract: The circulating milieu, bioactive molecules in the bloodstream, is altered with aging and interfaces constantly with the vasculature. This anatomic juxtaposition suggests that circulating factors may actively modulate arterial function. Here, we ... ...

Abstract	The circulating milieu, bioactive molecules in the bloodstream, is altered with aging and interfaces constantly with the vasculature. This anatomic juxtaposition suggests that circulating factors may actively modulate arterial function. Here, we developed a novel, translational experimental model that allows for direct interrogation of the influence of the circulating milieu on age-related arterial dysfunction (aortic stiffening and endothelial dysfunction). To do so, we exposed young and old mouse arteries to serum from young and old mice and young and midlife/older (ML/O) adult humans. We found that old mouse and ML/O adult human, but not young, serum stiffened young mouse aortic rings, assessed via elastic modulus (mouse and human serum,
MeSH term(s)	Animals ; Vascular Stiffness ; Humans ; Aging ; Male ; Mice, Inbred C57BL ; Adult ; Middle Aged ; Female ; Endothelium, Vascular/physiopathology ; Vasodilation ; Aged ; Age Factors ; Mice ; Aorta/physiopathology ; Carotid Arteries/physiopathology ; Young Adult ; Elastic Modulus
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00014.2024
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Article ; Online: Coronary Plaque Sampling Reveals Molecular Insights Into Coronary Artery Disease.

Widlansky, Michael E / Liu, Yong / Tumusiime, Shakirah / Hofeld, Benjamin / Khan, Nabeel / Aljadah, Michael / Wang, Jingli / Anger, Amberly / Qiu, Qiongzi / Therani, Bhavika / Liu, Pengyuan / Liang, Mingyu

Circulation research

2023 Volume 133, Issue 6, Page(s) 532–534

MeSH term(s)	Humans ; Coronary Artery Disease/genetics ; Plaque, Atherosclerotic ; Heart ; Coronary Vessels ; Coronary Angiography ; Risk Factors
Language	English
Publishing date	2023-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.123.323022
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Article: Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.

Ihenacho, Ugochukwu Kelvin / Meacham, Kelsey A / Harwig, Megan Cleland / Widlansky, Michael E / Hill, R Blake

Frontiers in endocrinology

2021 Volume 12, Page(s) 660095

Abstract: Mitochondrial fission protein 1 (Fis1) was identified in yeast as being essential for mitochondrial division or fission and subsequently determined to mediate human mitochondrial and peroxisomal fission. Yet, its exact functions in humans, especially in ... ...

Abstract	Mitochondrial fission protein 1 (Fis1) was identified in yeast as being essential for mitochondrial division or fission and subsequently determined to mediate human mitochondrial and peroxisomal fission. Yet, its exact functions in humans, especially in regard to mitochondrial fission, remains an enigma as genetic deletion of Fis1 elongates mitochondria in some cell types, but not others. Fis1 has also been identified as an important component of apoptotic and mitophagic pathways suggesting the protein may have multiple, essential roles. This review presents current perspectives on the emerging functions of Fis1 and their implications in human health and diseases, with an emphasis on Fis1's role in both endocrine and neurological disorders.
MeSH term(s)	Animals ; Endocrine System Diseases/genetics ; Endocrine System Diseases/metabolism ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Nervous System Diseases/genetics ; Nervous System Diseases/metabolism
Chemical Substances	FIS1 protein, human ; Membrane Proteins ; Mitochondrial Proteins
Language	English
Publishing date	2021-03-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.660095
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Article ; Online: The impact of standing desks on cardiometabolic and vascular health.

Bodker, Ariel / Visotcky, Alexis / Gutterman, David / Widlansky, Michael E / Kulinski, Jacquelyn

Vascular medicine (London, England)

2021 Volume 26, Issue 4, Page(s) 374–382

Abstract: Sedentary behavior is associated with cardiovascular disease (CVD) and mortality, independent of physical activity. The biological mechanisms underlying these associations are largely unknown. We hypothesized that obese subjects with sedentary desk jobs, ...

Abstract	Sedentary behavior is associated with cardiovascular disease (CVD) and mortality, independent of physical activity. The biological mechanisms underlying these associations are largely unknown. We hypothesized that obese subjects with sedentary desk jobs, when assigned a sit-stand desk, will reduce daily sedentary time, and show improvement in arterial flow-mediated dilation (FMD), an early indicator of CVD. Overweight and obese subjects without known CVD were recruited at our institution and given an adjustable sit-stand desk at work. Activities were quantified with an accelerometer for 7 days at baseline and during the intervention. FMD of the brachial and superficial femoral arteries, fasting lipids, insulin and glucose labs, and anthropometrics were measured at baseline, and 12 and 24 weeks. Repeated one-way ANOVA tests were used to compare measurements over time. Fifteen participants were enrolled (93% female, mean age 40 ± 5 years, mean body mass index [BMI] 33 ± 5). Mean daily sedentary time at work decreased by 90 minutes from baseline (385 ± 49 minutes) to 12 weeks (297 ± 80 minutes,
MeSH term(s)	Adult ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/prevention & control ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Obesity/diagnosis ; Sedentary Behavior ; Workplace
Language	English
Publishing date	2021-04-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1311628-9
ISSN	1477-0377 ; 1358-863X
ISSN (online)	1477-0377
ISSN	1358-863X
DOI	10.1177/1358863X211001934
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Article ; Online: The danger of sedenterism: endothelium at risk.

Widlansky, Michael E

American journal of physiology. Heart and circulatory physiology

2010 Volume 299, Issue 2, Page(s) H243–4

MeSH term(s)	Biomarkers/blood ; Blood Glucose/metabolism ; Cell-Derived Microparticles/pathology ; E-Selectin/blood ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; Humans ; Leg ; Lipids/blood ; Microcirculation ; Sedentary Behavior ; Skin/blood supply ; Vascular Endothelial Growth Factor A/blood ; Vascular Endothelial Growth Factor Receptor-1/blood ; Vasodilation
Chemical Substances	Biomarkers ; Blood Glucose ; E-Selectin ; Lipids ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; FLT1 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2010-05-28
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00505.2010
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Article: Acute effects of singing on cardiovascular biomarkers.

Somayaji, Kamila / Frenkel, Mogen / Tabaza, Luai / Visotcky, Alexis / Ruck, Tanya Kruse / Ofori, Ernest Kwesi / Widlansky, Michael E / Kulinski, Jacquelyn

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 869104

Abstract: Background: Singing is a physical activity involving components of the vagal nerves manifested as changes in cardiac autonomic regulation.: Aims: The aim of this pilot study is to investigate the acute effects of singing on biomarkers of ... ...

Abstract	Background: Singing is a physical activity involving components of the vagal nerves manifested as changes in cardiac autonomic regulation. Aims: The aim of this pilot study is to investigate the acute effects of singing on biomarkers of cardiovascular health. Methods: Adult subjects were recruited from cardiology clinics to participate in a single 90-min study visit. Vascular function was measured at the fingertips with peripheral arterial tonometry (PAT) before and after singing to a 14-min video led by a voice expert. Heart rate variability (HRV) was measured with a chest strap sensor at baseline, during, and after singing. PAT measurements were expressed as reactive hyperemia index (RHI) and Framingham reactive hyperemia index (fRHI). Measures of HRV included root mean square of successive RR interval differences (RMSSD) and standard deviation of NN (or RR) intervals (SDNN). Results: Sixty subjects completed the study (68% female, mean age 61 ±13 years, mean BMI 32 ± 8). There was a significant increase in fRHI (1.88 ± 0.14 to 2.10 ± 0.14, Conclusions: A short duration of singing improved vascular function acutely. Improvements were more substantial in subjects with abnormal baseline endothelial function. HRV patterns were similar to that of light-intensity exercise. Future studies should confirm favorable vascular adaptation to more sustained singing interventions. Clinical trial registration: ClinicalTrials.gov, identifer: NCT03805529.
Language	English
Publishing date	2022-07-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.869104
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