Protective Effect of Focal Adhesion Kinase against Skeletal Muscle Reperfusion Injury after Acute Limb Ischemia.

Flück, M; von Allmen, Regula; Ferrié, C; Tevaearai, Hendrik; Dick, Florian (2015). Protective Effect of Focal Adhesion Kinase against Skeletal Muscle Reperfusion Injury after Acute Limb Ischemia. European journal of vascular and endovascular surgery EJVES, 49(3), pp. 306-313. Elsevier 10.1016/j.ejvs.2014.11.011

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OBJECTIVES

In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too.

MATERIAL AND METHODS

In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls.

RESULTS

After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66).

CONCLUSIONS

IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery

UniBE Contributor:

von Allmen, Regula; Tevaearai, Hendrik and Dick, Florian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1078-5884

Publisher:

Elsevier

Language:

English

Submitter:

Sara Baumberger

Date Deposited:

17 Feb 2015 08:18

Last Modified:

11 Mar 2021 06:24

Publisher DOI:

10.1016/j.ejvs.2014.11.011

PubMed ID:

25556082

Uncontrolled Keywords:

Electroporation, Focal adhesion kinase, Gene transfer, Ischemia, Reperfusion injury

BORIS DOI:

10.7892/boris.63185

URI:

https://boris.unibe.ch/id/eprint/63185

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