Cardiac cannibalism
2014; Elsevier BV; Volume: 148; Issue: 6 Linguagem: Inglês
10.1016/j.jtcvs.2014.09.070
ISSN1097-685X
Autores Tópico(s)Neuroethics, Human Enhancement, Biomedical Innovations
ResumoSee related article on pages 3172-8. See related article on pages 3172-8. So, if you and a couple of guys are floating on a life raft in the middle of the Pacific and you are running out of food, what do you do? You throw the guy who eats the most overboard. Unless, of course, you can swallow both your pride and the big guy's liver. As it turns out, Drosophila figured out both of these steps millions of years ago … and autophagy has been evolutionarily conserved ever since. This remarkable self-preservation strategy is activated by both starvation and stress. Autophagy is a catabolic mechanism of degrading and disposing of dysfunctional cellular elements. Broken or profligate cytoplasmic constituents are herded into and isolated in a double-membraned vesicle imaginatively termed an autophagosome. This vesicle then fuses with a toxic, enzyme-laden lysosome, which spews its contents into the autophagosomal recycling container. The component parts of the previously worn-out cytoplasmic scaffolding can then be used to rebuild essential cellular machinery. But—like many good things—the autophagosome can go rogue and begin eating things that are not on the menu. In the study described in their article in this issue of the Journal of Thoracic and Cardiovascular Surgery, Sabe and colleagues1Sabe A.A. Elmadhun N.Y. Sadek A.A. Chu L.M. Bianchi C. Sellke F.W. Differential effects of atorvastatin in ischemic and non-ischemic myocardium in Ossabaw swine with metabolic syndrome.J Thorac Cardiovasc Surg. 2014; 148: 3172-3178Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar from the Sellke laboratory fed Ossabaw pigs a regular diet, a high-cholesterol diet, or the same high-cholesterol pâté plus a statin. The lipid-laden diet contained a “high-cholesterol” formula consisting of 4% cholesterol, 17.2% coconut oil, 2.3% corn oil, 1.5% sodium cholate, and 75% regular chow.2Elmadhun N.Y. Lassaletta A.D. Chu L.M. Liu Y. Feng J. Sellke F.W. Atorvastatin increases oxidative stress and modulates angiogenesis in Ossabaw swine with the metabolic syndrome.J Thorac Cardiovasc Surg. 2012; 144: 1486-1493Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Let's place this in perspective: a McDonald's Double Quarter Pounder With Cheese provides 277 grams of enjoyment with 749 calories, 42 grams of fat, and 165 mg of cholesterol.3McDonald's Corporation. McDonald's USA nutrition facts for popular menu items. Available at: http://nutrition.mcdonalds.com/getnutrition/nutritionfacts.pdf. Accessed September 19, 2014.Google Scholar So the pudgy pigs in this study got the equivalent of a couple of Quarter Pounders a day and probably thought they were starving. And these pigs paid the price of cholesterol-boosting gluttony with an associated decrease in protective autophagy. Interestingly, atorvastatin (not available to most pigs) preserved this highly-conserved evolutionary myocellular protective mechanism in nonischemic myocardium. Perhaps surprisingly, a statin had the opposite effect in the ischemic heart. Several aspects of this important article are fascinating: (1) for those of us type A cardiac surgical ascetics who are capable of sticking to a lifetime relatively healthy diet, in only 14 weeks of binge eating, we can blow the whole thing; (2) statins, which block the rate-limiting step in cholesterol synthesis, are also termed pleiotropic (which means that they also do lots of stuff that we don't understand); (3) for healthy nonischemic myocardium, autophagy seems to be an effective depository for component recycling and energy; and (4) a cardiomyocellular autophagosome in a male Ossabaw pig is kind of like the garbage disposal in the kitchen of a recycling center run by solar panels on the roof. Differential effects of atorvastatin on autophagy in ischemic and nonischemic myocardium in Ossabaw swine with metabolic syndromeThe Journal of Thoracic and Cardiovascular SurgeryVol. 148Issue 6PreviewThe perioperative administration of pleomorphic statin drugs has been implicated in improving outcomes after cardiac surgery. Adaptive autophagy is a highly conserved cellular process that allows for the elimination of dysfunctional cell components in response to stress and survival under starving conditions. We sought to investigate the effects of the statin drug atorvastatin on autophagy in ischemic and nonischemic myocardia using a clinically relevant porcine model of metabolic syndrome. Full-Text PDF Open Archive
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