Dysfunctional Wound Healing in Diabetic Foot Ulcers: New Crossroads

被引:316
作者
Davis, Frank M. [1 ]
Kimball, Andrew [1 ]
Boniakowski, Anna [1 ]
Gallagher, Katherine [1 ]
机构
[1] Univ Michigan, Dept Surg, Sect Vasc Surg, 5364 Cardiovasc Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA
关键词
Diabetes; Wound; Mechanism; Inflammation; Epigenetic; CIRCULATING ANGIOGENIC CELLS; MATRIX-METALLOPROTEINASES; METABOLIC MEMORY; DIFFERENTIAL EXPRESSION; IMPAIRED ANGIOGENESIS; MICE; COMPLICATIONS; HIF-1-ALPHA; MICRORNAS; MELLITUS;
D O I
10.1007/s11892-018-0970-z
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Purpose of Review Diabetic foot ulcerations (DFU) affect 25% of patients with diabetes mellitus during their lifetime and constitute a major health problem as they are often recalcitrant to healing due to a constellation of both intrinsic and extrinsic factors. The purpose of this review is to (1) detail the current mechanistic understanding of DFU formation and (2) highlight future therapeutic targets. Recent Findings From a molecular perspective, DFUs exhibit a chronic inflammatory predisposition. In addition, increased local hypoxic conditions and impaired cellular responses to hypoxia are pathogenic factors that contribute to delayed wound healing. Finally, recent evidence suggests a role for epigenetic alterations, including microRNAs, in delayed DFU healing due to the complex interplay between genes and the environment. Summary In this regard, notable progress has been made in the molecular and genetic understanding of DFU formation. However, further studies are needed to translate preclinical investigations into clinical therapies.
引用
收藏
页数:8
相关论文
共 76 条
[1]
[Anonymous], 2014, National diabetes statistics report
[2]
Diabetic Foot Ulcers and Their Recurrence [J].
Armstrong, David G. ;
Boulton, Andrew J. M. ;
Bus, Sicco A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (24) :2367-2375
[3]
The development of global consensus guidelines on the management and prevention of the diabetic foot 2011 [J].
Bakker, K. ;
Schaper, N. C. .
DIABETES-METABOLISM RESEARCH AND REVIEWS, 2012, 28 :116-118
[4]
Pathogenesis and Treatment of Impaired Wound Healing in Diabetes Mellitus: New Insights [J].
Baltzis, Dimitrios ;
Eleftheriadou, Ioanna ;
Veves, Aristidis .
ADVANCES IN THERAPY, 2014, 31 (08) :817-836
[5]
Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice [J].
Bannon, Pauline ;
Wood, Sally ;
Restivo, Terry ;
Campbell, Laura ;
Hardman, Matthew J. ;
Mace, Kimberly A. .
DISEASE MODELS & MECHANISMS, 2013, 6 (06) :1434-1447
[6]
The Chaperone-Dependent Ubiquitin Ligase CHIP Targets HIF-1α for Degradation in the Presence of Methylglyoxal [J].
Bento, Carla Figueira ;
Fernandes, Rosa ;
Ramalho, Jose ;
Marques, Carla ;
Shang, Fu ;
Taylor, Allen ;
Pereira, Paulo .
PLOS ONE, 2010, 5 (11)
[7]
Metabolic memory phenomenon in diabetes mellitus: Achieving and perspectives [J].
Berezin, Alexander .
DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS, 2016, 10 (02) :S176-S183
[8]
Stabilization of HIF-1α is critical to improve wound healing in diabetic mice [J].
Botusan, Ileana Ruxandra ;
Sunkari, Vivekananda Gupta ;
Savu, Octavian ;
Catrina, Anca Irinel ;
Grunler, Jacob ;
Lindberg, Stina ;
Pereira, Teresa ;
Yla-Herttuala, Seppo ;
Poellinger, Lorenz ;
Brismar, Kerstin ;
Catrina, Sergiu-Bogdan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (49) :19426-19431
[9]
Diabetic Foot Ulcer: An Evidence-Based Treatment Update [J].
Braun, Liza R. ;
Fisk, Whitney A. ;
Lev-Tov, Hadar ;
Kirsner, Robert S. ;
Isseroff, Roslyn R. .
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY, 2014, 15 (03) :267-281
[10]
Hyperglycentia regulates hypoxia-inducible factor-1α protein stability and function [J].
Catrina, SB ;
Okamoto, K ;
Pereira, T ;
Brismar, K ;
Poellinger, L .
DIABETES, 2004, 53 (12) :3226-3232