[en] BACKGROUND. The events that occur in the mitochondria play a key role in ischemic cardiomyopathy (IC). OBJECTIVES. The first objective of the study was to analyze the influence of major European haplogroups and polymorphisms that define the development of IC in a Spanish population. The second objective was to investigate the mitochondrial protein profile of a healthy ventricular region, adjacent to the site of infarction in a porcine model of ischemia and reperfusion (I/R). METHODS. To accomplish the first aim the polymorphisms that define the different mitochondrial haplogroups were detected in DNA samples of 423 controls and 358 patients with IC. For the second objective mitochondrial proteins were extracted from heart tissue from 11 pigs (Sus scrofa), 3 or 15 days after I/R. Changes in mitochondrial protein expression were detected and compared against non-operated pigs by tandem mass spectrometry. RESULTS. In the first study, haplogroup H was significantly overrepresented in the pathological group (OR=1.50, p<0.05) while the frequency of haplogroup J in the group of patients with IC was significantly lower compared against the control population (OR=0.47, p<0.05). In the analysis of the mitochondrial proteome, we identified 70 significantly regulated mitochondrial proteins. An increase in the expression of proteins involved in the electron transport chain and glycolysis were observed 3 days post I/R. This is a possible mechanism to compensate for the energy demand in the areas surrounding the lesion. Interestingly, the protein expression pattern had changed dramatically after 15 days, reverting to a similar pattern to that observed in control animals, suggesting a bias toward tissue stabilization. The overexpression of BRP44L, a pyruvate transporter that could be essential for the energy uptake after the ischemia, was validated for the first time. CONCLUSIONS. 1) This study has demonstrated for the first time that haplogroups with opposite phenotypes regarding the production of reactive oxygen species are respectively risk (H) and protective factors (J) for the development of IC. 2) Differences in mitochondrial proteomic profile 3 and 15 days post I/R have been determined showing an increase exprerssion of proteins involved with pyruvate transport, metabolism and energy production. An in-depth analysis of proteins detected in this study such as BRP44L, could be useful for the development of therapies aimed at stabilizing the myocardial tissue in post-ischemic stages.

[gl] FONDO. Os eventos que suceden na mitocondria xogan un papel fundamental na cardiopatía isquémica (CI). OBXECTIVOS. O primeiro obxectivo deste estudo foi analizar a influencia dos principais haplogrupos europeos e os polimorfismos que os definen sobre o desenvolvemento da CI nunha poboación española. O segundo obxectivo foi o de investigar o perfil proteico mitocondrial da rexión ventricular sá, próxima á zona de infarto nun modelo porcino de isquemia e reperfusíon (I/R). MÉTODOS. Para o primeiro obxectivo, detectáronse os polimorfismos que definen os distintos haplogrupos mitocondriais en mostras de ADN de 423 controles e 358 doentes con CI. Para o segundo extraéronse proteínas mitocondriais de texido cardíaco de 11 cerdos (Sus scorfa) 3 ou 15 días tras o procedemento de I/R. Os cambios na expresión das proteínas mitocondriais con respecto ó grupo control de cerdos sen operar foron detectados mediante espectometría de masas en tándem. RESULTADOS. No primeiro estudo, o haplogrupo H atopouse significativamente máis representado no grupo patolóxico (OR=1,50, p<0,05) ao mesmo tempo que a frecuencia do haplogrupo J no grupo de doentes con CI foi significativamente menor que na poboación control (OR=0,47, p<0,05). No análise do proteoma mitocondrial identificarónse 70 proteínas mitocondriais significativamente reguladas. Observouse un incremento da expresión de proteínas implicadas na cadena de transporte de eletróns e na glucólise ós 3 días como posible mecanismo para compensar a demanda enerxética das zonas próximas á lesión. Ós 15 días o patrón proteico revertiu a un máis próximo ó observado en animais control, suxerindo un sesgo cara a estabilización do texido. Validóuse por primeira vez a sobreexpresión da proteina BRP44L, un transportador de piruvato que poderia ser esencial para a obtención de enerxia tras a isquemia. CONCLUSIÓNS. 1) Demostrouse por primeira vez que haplogrupos con fenótipos opostos en relación á produción de especies reactivas de osíxeno son, respectivamente, factores de risco (H) e de protección (J) para o desenvolvemento da CI. 2) Determináronse diferencias no perfil proteico mitocondrial 3 e 15 días tras a I/R amosando un aumento de proteínas de transporte e metabolismo de piruvato e involucradas na producción de enerxía. O estudo en profundidade das proteínas detectadas neste estudo, coma BRP44L, poderían ser utilies para o desenvolvemento de terapias enfocadas á estabilización do texido miocárdico en etapas post-isquémicas.