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Article ; Online: Praliciguat and Soluble Guanylate Cyclase Stimulators for Peripheral Artery Disease.

Kosmac, Kate / Ismaeel, Ahmed / Kim-Shapiro, Daniel B / McDermott, Mary M

2023 Volume 132, Issue 1, Page(s) 49–51

MeSH term(s)	Humans ; Soluble Guanylyl Cyclase ; Guanylate Cyclase ; Vasodilator Agents ; Peripheral Arterial Disease/drug therapy ; Nitric Oxide ; Cyclic GMP
Chemical Substances	Soluble Guanylyl Cyclase (EC 4.6.1.2) ; praliciguat (R1S0H458SA) ; Guanylate Cyclase (EC 4.6.1.2) ; Vasodilator Agents ; Nitric Oxide (31C4KY9ESH) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2023-01-05
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.122.322298
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Article ; Online: Cocoa flavanols, Nrf2 activation, and oxidative stress in peripheral artery disease: mechanistic findings in muscle based on outcomes from a randomized trial.

Ismaeel, Ahmed / McDermott, Mary M / Joshi, Jai K / Sturgis, Jada C / Zhang, Dongxue / Ho, Karen J / Sufit, Robert / Ferrucci, Luigi / Peterson, Charlotte A / Kosmac, Kate

American journal of physiology. Cell physiology

2024 Volume 326, Issue 2, Page(s) C589–C605

Abstract: The pathophysiology of muscle damage in peripheral artery disease (PAD) includes increased oxidant production and impaired antioxidant defenses. Epicatechin (EPI), a naturally occurring flavanol, has antioxidant properties that may mediate the beneficial ...

Abstract	The pathophysiology of muscle damage in peripheral artery disease (PAD) includes increased oxidant production and impaired antioxidant defenses. Epicatechin (EPI), a naturally occurring flavanol, has antioxidant properties that may mediate the beneficial effects of natural products such as cocoa. In a phase II randomized trial, a cocoa-flavanol-rich beverage significantly improved walking performance compared with a placebo in people with PAD. In the present work, the molecular mechanisms underlying the therapeutic effect of cocoa flavanols were investigated by analyzing baseline and follow-up muscle biopsies from participants. Increases in nuclear factor erythroid 2-related factor 2 (Nrf2) target antioxidants heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) in the cocoa group were significantly associated with reduced accumulation of central nuclei, a myopathy indicator, in type II muscle fibers (
MeSH term(s)	Humans ; Antioxidants/metabolism ; Antioxidants/pharmacology ; Cacao/chemistry ; Catechin/metabolism ; Catechin/pharmacology ; Heme Oxygenase-1/metabolism ; Heme Oxygenase-1/pharmacology ; Muscles ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; Peripheral Arterial Disease/drug therapy ; Peripheral Arterial Disease/metabolism ; Polyphenols/metabolism ; Polyphenols/pharmacology
Chemical Substances	Antioxidants ; Catechin (8R1V1STN48) ; Heme Oxygenase-1 (EC 1.14.14.18) ; NF-E2-Related Factor 2 ; Polyphenols
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase II ; Journal Article
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00573.2023
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Article: Potential Benefits of Combined Statin and Metformin Therapy on Resistance Training Response in Older Individuals.

Long, Douglas E / Kosmac, Kate / Dungan, Cory M / Bamman, Marcas M / Peterson, Charlotte A / Kern, Philip A

Frontiers in physiology

2022 Volume 13, Page(s) 872745

Abstract: Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has ... ...

Abstract	Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks of progressive resistance training (PRT) when compared to identical placebo treatment (
Language	English
Publishing date	2022-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.872745
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Article: Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-invasive Anterior Cruciate Ligament Injury.

Davi, Steven M / Ahn, Ahram / White, McKenzie S / Butterfield, Timothy A / Kosmac, Kate / Kwon, Oh Sung / Lepley, Lindsey K

Frontiers in physiology

2022 Volume 13, Page(s) 805213

Abstract: Introduction: Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature ... ...

Abstract	Introduction: Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions. Methods: A total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex. Results: Mitochondria-derived ROS increased from days 7 to 56 after ACL injury (30-100%, Conclusion: Long-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury.
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.805213
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Article ; Online: Mitochondrial Complex Abundance, Mitophagy Proteins, and Physical Performance in People With and Without Peripheral Artery Disease.

Picca, Anna / Wohlgemuth, Stephanie E / McDermott, Mary M / Saini, Sunil K / Dayanidhi, Sudarshan / Zhang, Dongxue / Xu, Shujun / Kosmac, Kate / Tian, Lu / Ferrucci, Luigi / Sufit, Robert L / Marzetti, Emanuele / Leeuwenburgh, Christiaan

Journal of the American Heart Association

2023 Volume 12, Issue 6, Page(s) e027088

Abstract: Background Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is ... ...

Abstract	Background Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. Methods and Results Protein markers of mitochondrial biogenesis and autophagy and the abundance of mitochondrial electron transport chain complexes were quantified in gastrocnemius muscle biopsies from people with and without PAD. Their 6-minute walk distance and 4-m gait speed were measured. Sixty-seven participants (mean age 65.0 years [±6.8], 16 [23.9%] women, 48 [71.6%] Black) were enrolled, including 15 with moderate to severe PAD (ankle brachial index [ABI] <0.60), 29 with mild PAD (ABI 0.60-0.90), and 23 without PAD (ABI 1.00-1.40). Abundance of all electron transport chain complexes was significantly higher in participants with lower ABI (eg, complex I: 0.66, 0.45, 0.48 arbitrary units [AU], respectively,
MeSH term(s)	Humans ; Female ; Aged ; Male ; Mitophagy ; Peripheral Arterial Disease/diagnosis ; Walking/physiology ; Ankle Brachial Index ; Ischemia ; Microtubule-Associated Proteins ; Physical Functional Performance
Chemical Substances	Microtubule-Associated Proteins
Language	English
Publishing date	2023-03-09
Publishing country	England
Document type	Journal Article ; 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.122.027088
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Article: Construct and criterion validity of muscle ultrasonography for assessment of skeletal muscle in patients recovering from COVID-19.

Mayer, Kirby P / Kosmac, Kate / Wen, Yuan / Parry, Selina M / Dhar, Sanjay / Foster, Sarah / Starck, Jonathan / Montgomery-Yates, Ashley A / Dupont-Versteegden, Esther E / Kalema, Anna G

Frontiers in physiology

2023 Volume 14, Page(s) 1231538

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-10-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1231538
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Article ; Online: Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease.

McDermott, Mary M / Dayanidhi, Sudarshan / Kosmac, Kate / Saini, Sunil / Slysz, Joshua / Leeuwenburgh, Christiaan / Hartnell, Lisa / Sufit, Robert / Ferrucci, Luigi

Circulation research

2021 Volume 128, Issue 12, Page(s) 1851–1867

Abstract: Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of ... ...

Abstract	Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of walking exercise on lower extremity skeletal muscle in PAD. In older people without PAD, aerobic exercise improves mitochondrial activity, muscle mass, capillary density, and insulin sensitivity in skeletal muscle. However, walking exercise increases lower extremity ischemia in people with PAD, and therefore, mechanisms by which this exercise improves walking may differ between people with and without PAD. Compared with people without PAD, gastrocnemius muscle in people with PAD has greater mitochondrial impairment, increased reactive oxygen species, and increased fibrosis. In multiple small trials, walking exercise therapy did not consistently improve mitochondrial activity in people with PAD. In one 12-week randomized trial of people with PAD randomized to supervised exercise or control, supervised treadmill exercise increased treadmill walking time from 9.3 to 15.1 minutes, but simultaneously increased the proportion of angular muscle fibers, consistent with muscle denervation (from 7.6% to 15.6%), while angular myofibers did not change in the control group (from 9.1% to 9.1%). These findings suggest an adaptive response to exercise in PAD that includes denervation and reinnervation, an adaptive process observed in skeletal muscle of people without PAD during aging. Small studies have not shown significant effects of exercise on increased capillary density in lower extremity skeletal muscle of participants with PAD, and there are no data showing that exercise improves microcirculatory delivery of oxygen and nutrients in patients with PAD. However, the effects of supervised exercise on increased plasma nitrite abundance after a treadmill walking test in people with PAD may be associated with improved lower extremity skeletal muscle perfusion and may contribute to improved walking performance in response to exercise in people with PAD. Randomized trials with serial, comprehensive measures of muscle biology, and physiology are needed to clarify mechanisms by which walking exercise interventions improve mobility in PAD.
MeSH term(s)	Age Factors ; Aging ; Animals ; Capillaries/anatomy & histology ; Exercise/physiology ; Exercise Therapy/methods ; Humans ; Ischemia/etiology ; Lower Extremity/blood supply ; Mice ; Microcirculation ; Mitochondria, Muscle/physiology ; Muscle Denervation ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/blood supply ; Muscle, Skeletal/innervation ; Muscle, Skeletal/physiology ; Neuromuscular Junction/physiology ; Peripheral Arterial Disease/complications ; Peripheral Arterial Disease/therapy ; Randomized Controlled Trials as Topic ; Reactive Oxygen Species/metabolism ; Time Factors ; Walking/physiology
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2021-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.121.318242
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Article ; Online: Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice.

Seleme, Maria C / Kosmac, Kate / Jonjic, Stipan / Britt, William J

Journal of virology

2017 Volume 91, Issue 8

Abstract: Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more ... ...

Abstract	Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45
MeSH term(s)	Animals ; Animals, Newborn ; Brain/growth & development ; Brain/pathology ; Cytokines/analysis ; Cytomegalovirus Infections/congenital ; Cytomegalovirus Infections/pathology ; Disease Models, Animal ; Inflammation/pathology ; Leukocytes, Mononuclear/immunology ; Mice ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Cytokines ; Tumor Necrosis Factor-alpha
Keywords	covid19
Language	English
Publishing date	2017-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01983-16
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Article ; Online: A muscle cell-macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading.

Peck, Bailey D / Murach, Kevin A / Walton, R Grace / Simmons, Alexander J / Long, Douglas E / Kosmac, Kate / Dungan, Cory M / Kern, Philip A / Bamman, Marcas M / Peterson, Charlotte A

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

2022 Volume 36, Issue 2, Page(s) e22155

Abstract: The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older ... ...

Abstract	The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single-cell RNA-seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell-macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.
MeSH term(s)	Adult ; Aged ; Animals ; Cells, Cultured ; Collagen Type I/metabolism ; Extracellular Matrix/metabolism ; Female ; Humans ; Leukemia Inhibitory Factor/metabolism ; Leukocytes, Mononuclear/metabolism ; Macrophages/metabolism ; Male ; Matrix Metalloproteinase 14/metabolism ; Mice ; Muscle Contraction/physiology ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/metabolism ; Resistance Training/methods
Chemical Substances	Collagen Type I ; Leukemia Inhibitory Factor ; MMP14 protein, human (EC 3.4.24.80) ; Matrix Metalloproteinase 14 (EC 3.4.24.80)
Language	English
Publishing date	2022-01-19
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.202100182RR
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Article ; Online: Skeletal muscle properties show collagen organization and immune cell content are associated with resistance exercise response heterogeneity in older persons.

Long, Douglas E / Peck, Bailey D / Lavin, Kaleen M / Dungan, Cory M / Kosmac, Kate / Tuggle, Steven C / Bamman, Marcas M / Kern, Philip A / Peterson, Charlotte A

Journal of applied physiology (Bethesda, Md. : 1985)

2022 Volume 132, Issue 6, Page(s) 1432–1447

Abstract: In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish novel relationships between baseline muscle features ... ...

Abstract	In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish novel relationships between baseline muscle features and/or their PRT-induced change in vastus lateralis muscle biopsies with hypertrophy outcomes. Multiple linear regression analyses adjusted for sex were performed on phenotypic data from older adults (
MeSH term(s)	Aged ; Aged, 80 and over ; Collagen ; Female ; Humans ; Hypertrophy ; Male ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/physiology ; Resistance Training
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00025.2022
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