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Property "Has-20abstract" (as page type) with input value "Progressive-20energy-20deficiency-20and-20loss-20of-20cardiomyocyte-20numbers-20are-20two-20prominent-20factors-20that-20lead-20to-20heart-20failure-20in-20experimental-20models.-20Signals-20which-20mediate-20cardiomyocyte-20cell-20death-20have-20been-20suggested-20to-20come-20from-20both-20extrinsic-20(e.g.-20cytokines)-20and-20intrinsic-20(e.g.-20mitochondria)-20sources,-20but-20the-20evidence-20supporting-20these-20mechanisms-20remain-20unclear,-20and-20virtually-20non-2Dexistent-20in-20humans.-20In-20this-20study,-20we-20investigated-20the-20sensitivity-20of-20the-20mitochondrial-20permeability-20transition-20pore-20(mtPTP)-20to-20calcium-20(Ca-3Csup-3E2+-3C-2Fsup-3E)-20using-20permeabilized-20myofibers-20of-20right-20atrium-20obtained-20from-20diabetic-20(-27-27N-27-27-20=-209)-20and-20non-2Ddiabetic-20(-27-27N-27-27-20=-2012)-20patients-20with-20coronary-20artery-20disease-20undergoing-20non-2Demergent-20coronary-20revascularization-20surgery.-20Under-20conditions-20that-20mimic-20the-20energetic-20state-20of-20the-20heart-20-27-27in-20vivo-27-27-20(pyruvate,-20glutamate,-20malate-20and-20100-20μM-20ADP),-20cardiac-20mitochondria-20from-20diabetic-20patients-20show-20an-20increased-20sensitivity-20to-20Ca-3Csup-3E2+-3C-2Fsup-3E-2Dinduced-20mtPTP-20opening-20as-20compared-20to-20non-2Ddiabetic-20patients.-20This-20increased-20mtPTP-20Ca-3Csup-3E2+-3C-2Fsup-3E-2Dsensitivity-20in-20diabetic-20heart-20mitochondria-20is-20accompanied-20by-20a-20substantially-20greater-20rate-20of-20mitochondrial-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission-20(mtH-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E)-20under-20identical-20conditions,-20despite-20no-20differences-20in-20respiratory-20capacity-20under-20these-20conditions-20or-20mitochondrial-20enzyme-20content.-20Activity-20of-20the-20intrinsic-20apoptosis-2Dpathway-20mediator,-20caspase-2D9,-20was-20greater-20in-20diabetic-20atrial-20tissue,-20while-20activity-20of-20the-20extrinsic-2Dpathway-20mediator,-20caspase-2D8,-20was-20unchanged-20between-20groups.-20Furthermore,-20caspase-2D3-20activity-20was-20not-20significantly-20increased-20in-20diabetic-20atrial-20tissue.-20These-20data-20collectively-20suggest-20that-20the-20myocardium-20in-20diabetic-20patients-20has-20a-20greater-20overall-20propensity-20for-20mitochondrial-2Ddependent-20cell-20death,-20possibly-20as-20a-20result-20of-20metabolic-20stress-2Dimposed-20changes-20that-20have-20occurred-20within-20the-20mitochondria,-20rendering-20them-20more-20susceptible-20to-20insults-20such-20as-20Ca-3Csup-3E2+-3C-2Fsup-3E-20overload.-20In-20addition,-20they-20lend-20further-20support-20to-20the-20notion-20that-20mitochondria-20represent-20a-20viable-20target-20for-20future-20therapies-20directed-20at-20ameliorating-20heart-20failure-20and-20other-20co-2Dmorbidities-20that-20come-20with-20diabetes." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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