Caspi 2020 J Am Heart Assoc
| Caspi T, Straw S, Cheng C, Garnham JO, Scragg JL, Smith J, Koshy AO, Levelt E, Sukumar P, Gierula J, Beech DJ, Kearney MT, Cubbon RM, Wheatcroft SB, Witte KK, Roberts LD, Bowen TS (2020) Unique transcriptome signature distinguishes patients with heart failure with myopathy. J Am Heart Assoc 9:e017091. https://doi.org/10.1161/JAHA.120.017091 |
Caspi T, Straw S, Cheng C, Garnham JO, Scragg JL, Smith Jessica, Koshy AO, Levelt E, Sukumar P, Gierula J, Beech DJ, Kearney MT, Cubbon RM, Wheatcroft SB, Witte KK, Roberts LD, Bowen TS (2020) J Am Heart Assoc
Abstract: Background: People with chronic heart failure (CHF) experience severe skeletal muscle dysfunction, characterized by mitochondrial abnormalities, which exacerbates the primary symptom of exercise intolerance. However, the molecular triggers and characteristics underlying mitochondrial abnormalities caused by CHF remain poorly understood.
Methods and Results: We recruited 28 patients with CHF caused by reduced ejection fraction and 9 controls. We simultaneously biopsied skeletal muscle from the pectoralis major in the upper limb and from the vastus lateralis in the lower limb. We phenotyped mitochondrial function in permeabilized myofibers from both sites and followed this by complete RNA sequencing to identify novel molecular abnormalities in CHF skeletal muscle. Patients with CHF presented with upper and lower limb skeletal muscle impairments to mitochondrial function that were of a similar deficit and indicative of a myopathy. Mitochondrial abnormalities were strongly correlated to symptoms. Further RNA sequencing revealed a unique transcriptome signature in CHF skeletal muscle characterized by a novel triad of differentially expressed genes related to deficits in energy metabolism including adenosine monophosphate deaminase 3, pyridine nucleotide‐disulphide oxidoreductase domain 2, and lactate dehydrogenase C.
Conclusions: Our data suggest an upper and lower limb metabolic myopathy that is characterized by a unique transcriptome signature in skeletal muscle of humans with CHF.
• Bioblast editor: Gnaiger E
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine
Pathology: Cardiovascular, Myopathy
Organism: Human Tissue;cell: Heart, Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, CIV, NS
HRR: Oxygraph-2k
VO2max
