Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Victoria R PalzkillDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0000-0001-9382-169X
Divyansha MoparthyDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.
Qingping YangDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0000-0002-6261-7861
Jaewon ChoiDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0009-0000-5298-4943
Xinyue LiuPharmacology and Therapeutics (X.L., A.B.A., D.K.), University of Florida, Gainesville, FL.ORCID 0009-0001-1004-4168
Kyoungrae KimDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0000-0001-9513-6469
Ambili B AppuPharmacology and Therapeutics (X.L., A.B.A., D.K.), University of Florida, Gainesville, FL.ORCID 0009-0005-3543-9229
Caroline G PassDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0009-0003-4234-8777
Scott A BerceliSurgery (S.A.B., S.T.S.), University of Florida, Gainesville, FL.ORCID 0000-0003-2257-0111
Curt D SigmundDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI (C.D.S.).ORCID 0000-0002-1453-0921
Salvatore T ScaliSurgery (S.A.B., S.T.S.), University of Florida, Gainesville, FL.ORCID 0000-0002-8128-3203
Daniel KopinkePharmacology and Therapeutics (X.L., A.B.A., D.K.), University of Florida, Gainesville, FL.ORCID 0000-0001-5148-8219
Terence E RyanDepartments of Applied Physiology and Kinesiology (V.R.P., D.M., Q.Y., J.C., K.K., C.G.P., T.E.R.), University of Florida, Gainesville, FL.ORCID 0000-0003-0780-029X
Funding
PPARG-dependent Mechanisms Control Endothelial-Smooth Muscle Coordination, Arterial Pressure, Vasomotor Function and Arterial StiffnessR35HL144807 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SIGMUND, CURT DANIEL · 2019 to 2024
$5.5M
Molecular mechanisms regulating peripheral arterial disease pathobiology in chronic kidney diseaseR01HL149704 · NHLBI · UNIVERSITY OF FLORIDA · PI Terence E Ryan · 2020 to 2026
$3.6M
Constitutive and Agent-Based Multiscale Models to Improve Vein Graft SurvivalU01HL119178 · NHLBI · UNIVERSITY OF FLORIDA · PI BERCELI, SCOTT A, GARBEY, MARC · 2013 to 2018
$2.7M
Impaired Mitochondrial Energetics is a Driver of Hemodialysis Access Related Hand DysfunctionR01HL148597 · NHLBI · UNIVERSITY OF FLORIDA · PI SCALI, SALVATORE T. · 2019 to 2023
$2.7M
Hemodynamics and Vascular Wall Biology Determine Arteriovenous Fistula MaturationR01DK088777 · NIDDK · UNIVERSITY OF UTAH · PI BERCELI, SCOTT A, CHEUNG, ALFRED K · 2011 to 2014
$2.6M
STUDENTS IN HEALTH PROFESSIONAL SCHOOLST35HL007489 · NHLBI · UNIVERSITY OF FLORIDA · PI Scott A Berceli, Robert Maile · 1985 to 2026
$2.4M
Translational and Computational Analysis of Dialysis Fistula Maturation Failure-2R01DK119274 · NIDDK · UNIVERSITY OF FLORIDA · PI BERCELI, SCOTT A · 2019 to 2022
$2.2M
Intersection of the PPARγ-RhoBTB1-Cullin-3 Pathway and Renin-Angiotensin System in Blood Pressure, Vascular Function and Arterial StiffnessR35HL177123 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Curt Daniel Sigmund · 2025 to 2026
$2.2M
The role of fatty fibrosis in chronic limb threatening ischemia pathobiologyR01HL171050 · NHLBI · UNIVERSITY OF FLORIDA · PI Daniel Kopinke, Terence E Ryan · 2024 to 2026
$2.0M
Interdisciplinary Training for Vascular Surgeon ScientistsT32HL160491 · NHLBI · UNIVERSITY OF FLORIDA · PI Scott A Berceli, Gilbert Rivers Upchurch · 2022 to 2026
$1.6M
Multiscale Network Modeling of Hemodynamically-Driven Vascular AdaptationR01HL095508 · NHLBI · UNIVERSITY OF FLORIDA · PI BERCELI, SCOTT A · 2009 to 2012
$1.5M
Mechanisms of Shear-Regulated Vein Graft RemodelingK08HL076453 · NHLBI · UNIVERSITY OF FLORIDA · PI BERCELI, SCOTT A · 2004 to 2008
backgroundPeripheral artery disease (PAD) and its severe form, chronic limb-threatening ischemia (CLTI), significantly impair blood flow to the lower extremities, affecting millions of adults globally. Intramuscular adipose tissue (IMAT) and fibrosis accumulation distinguish patients with CLTI from those with mild PAD, suggesting a role in CLTI pathobiology. However, the functional consequences of IMAT in CLTI remain unclear.
methodsWe compared gastrocnemius muscle samples from patients with PAD/CLTI, those with intermittent claudication, and non-PAD individuals. We analyzed bulk RNA sequencing, proteomic, lipidomic, and single-cell/nucleus RNA sequencing datasets. Additionally, we used murine models of hindlimb ischemia with genetic manipulation of Pparγ, a key adipogenic transcription factor, specifically in fibroadipogenic progenitor cells, the cellular source of IMAT, to modulate IMAT formation and assessed the impact on limb function and pathology.
resultsPatients with CLTI exhibited significantly elevated expression of adipogenic genes and proteins in muscle specimens when compared with non-PAD controls. Murine models showed that increasing IMAT formation significantly worsened ischemic limb muscle strength and work output. In contrast, preventing IMAT formation significantly improved ischemic limb muscle strength and work output. These findings were consistent across both male and female mice, although females had a greater tendency to form IMAT compared with male mice.
conclusionsIMAT accumulation is a key determinant of limb function in PAD/CLTI. Our studies demonstrate that targeting IMAT formation could improve limb function in mice with experimental PAD. Together, these findings suggest that developing strategies to limit or reduce IMAT may improve limb function and walking performance in patients with PAD/CLTI, providing a novel therapeutic avenue to address a critical unmet need.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.