Reduced cardiac CapZ protein protects hearts against acute ischemia–reperfusion injury and enhances preconditioning

Yang, Feng; Pyle, W. Glen

doi:10.1016/j.yjmcc.2011.11.013

Cited by 24 publications

(35 citation statements)

References 51 publications

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“…We propose that the reduction in myofilament-associated PKC␣ allows the myofilament complex to function with less hindrance by PKC␣ but that transient activation of myofilament-associated PKC␣ during I/R provides a cardioprotective advantage, possibly through an energy sparing mechanism (51). This hypothetical model incorporates the importance of both timing and subcellular localization of PKC activation, as has been advanced elsewhere (14,69). The time-dependent changes in PKC isoform translocation to the myofilaments are interesting and suggestive of a dynamic system during I/R.…”

Section: Discussionmentioning

confidence: 91%

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

Manning

Perkins

Sinclair

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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JJ. Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction. Am J Physiol Heart Circ Physiol 304: H1382-H1396, 2013. First published March 11, 2013 doi:10.1152/ajpheart.00613.2012.-Among its many biological roles, fibroblast growth factor-2 (FGF2) acutely protects the heart from dysfunction associated with ischemia/reperfusion (I/R) injury. Our laboratory has demonstrated that this is due to the activity of the low molecular weight (LMW) isoform of FGF2 and that FGF2-mediated cardioprotection relies on the activity of protein kinase C (PKC); however, which PKC isoforms are responsible for LMW FGF2-mediated cardioprotection, and their downstream targets, remain to be elucidated. To identify the PKC pathway(s) that contributes to postischemic cardiac recovery by LMW FGF2, mouse hearts expressing only LMW FGF2 (HMWKO) were bred to mouse hearts not expressing PKC␣ (PKC␣KO) or subjected to a selective PKCε inhibitor (εV1-2) before and during I/R. Hearts only expressing LMW FGF2 showed significantly improved postischemic recovery of cardiac function following I/R (P Ͻ 0.05), which was significantly abrogated in the absence of PKC␣ (P Ͻ 0.05) or presence of PKCε inhibition (P Ͻ 0.05). Hearts only expressing LMW FGF2 demonstrated differences in actomyosin ATPase activity as well as increases in the phosphorylation of troponin I and T during I/R compared with wild-type hearts; several of these effects were dependent on PKC␣ activity. This evidence indicates that both PKC␣ and PKCε play a role in LMW FGF2-mediated protection from cardiac dysfunction and that PKC␣ signaling to the contractile apparatus is a key step in the mechanism of LMW FGF2-mediated protection against myocardial dysfunction. low molecular weight FGF2; PKC␣ and ε; troponin; actomyosin ATPase; postischemic cardiac function CARDIOVASCULAR DISEASE IS the number one killer in the U.S., and every year over eight million people in the U.S. suffer from myocardial infarction (43). Often, myocardial ischemia is characterized by lowered postischemic left ventricular function, which is associated with increased morbidity and mortality (7). There is a profound and immediate need to address the problem of myocardial dysfunction and infarction associated with cardiac ischemia and reperfusion (I/R). One promising therapeutic strategy to alleviate I/R-induced cardiac injury is fibroblast growth factor-2 (FGF2).FGF2, found at elevated levels in the serum of I/R patients (63), has both angiogenic and acute cardioprotective effects (6,26,37,54,64). This makes FGF2 an outstanding candidate for the treatment of cardiac patients; however, while in recent years, there have been a number of noteworthy developments characterizing the mechanism of action of FGF2 in the ischemic heart, there are several unanswered questions that must be addressed before FGF2 becomes a therapeutic molecule. Yet to be determined is the distinct role each FGF2 isoform plays in the ischemic heart. FGF2...

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Section: Discussionmentioning

confidence: 91%

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

Manning

Perkins

Sinclair

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…The role of nPKC␦ is controversial, since both protective and detrimental roles have been described (370, 551, 759). Interestingly, an increase in intracellular Ca 2ϩ by itself can mediate ischemic preconditioning (568), and there is strong evidence that the protective effect is mediated by activation of the Ca 2ϩ -dependent cPKC␣ isozyme (78,333,440,617,817,893,908,923 FIGURE 13. Different subtypes of K ATP channels may synergistically interact to protect the heart against stress and ischemic insults.…”

Section: Mechanisms By Which K Atp Channels Protect Against Ischemic mentioning

confidence: 99%

K_ATPChannels in the Cardiovascular System

Foster

Coetzee

2016

Physiological Reviews

204

237

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KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease.

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“…4). The balloon and pressure transducer system used was that described by Yang and Pyle (Yang and Pyle, 2012). Platinum electrodes were placed on the atrium to pace the heart at 32 beats min −1 .…”

Section: Measurement Of Ventricular Pressure Generation Using Langendmentioning

confidence: 99%

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

Klaiman

Pyle

Gillis

2014

Journal of Experimental Biology

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Reducing temperature below the optimum of most vertebrate hearts impairs contractility and reduces organ function. However, a number of fish species, including the rainbow trout, can seasonally acclimate to low temperature. Such ability requires modification of physiological systems to compensate for the thermodynamic effects of temperature on biological processes. The current study tested the hypothesis that rainbow trout compensate for the direct effect of cold temperature by increasing cardiac contractility during cold acclimation. We examined cardiac contractility, following thermal acclimation (4, 11 and 17°C), by measuring the Ca 2+ sensitivity of force generation by chemically skinned cardiac trabeculae as well as ventricular pressure generation using a modified Langendorff preparation. We demonstrate, for the first time, that the Ca 2+ sensitivity of force generation was significantly higher in cardiac trabeculae from 4°C-acclimated trout compared with those acclimated to 11 or 17°C, and that this functional change occurred in parallel with a decrease in the level of cardiac troponin T phosphorylation. In addition, we show that the magnitude and rate of ventricular pressure generation was greater in hearts from trout acclimated to 4°C compared with those from animals acclimated to 11 or 17°C. Taken together, these results suggest that enhanced myofilament function, caused by modification of existing contractile proteins, is at least partially responsible for the observed increase in pressure generation after acclimation to 4°C. In addition, by examining the phenotypic plasticity of a comparative model we have identified a strategy, used in vivo, by which the force-generating capacity of cardiac muscle can be increased.

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Reduced cardiac CapZ protein protects hearts against acute ischemia–reperfusion injury and enhances preconditioning

Cited by 24 publications

References 51 publications

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

K_ATPChannels in the Cardiovascular System

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

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Reduced cardiac CapZ protein protects hearts against acute ischemia–reperfusion injury and enhances preconditioning

Cited by 24 publications

References 51 publications

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction

KATPChannels in the Cardiovascular System

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

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K_ATPChannels in the Cardiovascular System