Gene Transfer of Heat-Shock Protein 70 Reduces Infarct Size In Vivo After Ischemia/Reperfusion in the Rabbit Heart

Okubo, Seiji; Wildner, Oliver; Shah, Maulik; Chelliah, Jeya; Heß, Michael; Kukreja, Rakesh C.

doi:10.1161/01.cir.103.6.877

Cited by 120 publications

(88 citation statements)

References 46 publications

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“…For example, transgenic overexpression of HSP70 in the myocardium confers protection against both myocar- dial stunning and infarction following ischemia (14,21,28,30,42), whereas pharmacological induction of HSP70 in the myocardium also imparts resistance to ischemia (15,20,29,46). Furthermore, heat stress induction of HSP70 in the myocardium is associated with the development of "cross tolerance" to subsequent prolonged ischemia (4,43).…”

Section: Discussionmentioning

confidence: 99%

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

Hampton

Shimamoto

Rothnie

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionmentioning

confidence: 99%

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

Hampton

Shimamoto

Rothnie

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…TLR2 is known to recognize Hsp-60 and Hsp-70 (6,150,151) and hyaluronan (68). Some of these endogenous molecules such as Hsp-60 and Hsp-70 are produced in response to myocardial ischemia (78,95) and confer potent antiapoptotic and cardioprotective effects in the heart (66,68,76,115). It remains unclear, however, and would be of great importance to investigate whether or not TLRs mediate the cardiac benefit induced by these molecular chaperons and how to reconcile these findings with the suggested role of TLRs in I/R injury in the aforementioned loss-offunction studies.…”

Section: Tlr Signaling Mediates Myocardial I/r Injurymentioning

confidence: 99%

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

Chao¹

2009

American Journal of Physiology-Heart and Circulatory Physiology

212

166

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Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart.

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“…clusterin (77), serpins (78), hsp70 (79,80)). This is consistent with the idea that the IGF1-PI3K(p110␣) pathway is involved with promoting cell survival.…”

Section: Igf1r Induces Physiological Cardiac Growth Via Pi3k(p110␣)mentioning

confidence: 99%

The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway

McMullen

Shioi

Huang

et al. 2004

Journal of Biological Chemistry

374

325

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Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the treatment of heart failure. However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial. Secondary effects of increased serum IGF1 levels on other tissues may explain these unfavorable results. The aim of the current study was to examine the role of IGF1 in cardiac myocytes in the absence of secondary effects, and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic function at 3 months of age, and this was maintained at 12-16 months of age. The phosphoinositide 3-kinase (PI3K)-Aktp70S6K1 pathway was significantly activated in hearts from IGF1R transgenics. Cardiac hypertrophy induced by overexpression of IGF1R was completely blocked by a dominant negative PI3K(p110␣) mutant, suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110␣)-dependent manner. This study suggests that targeting the cardiac IGF1R-PI3K(p110␣) pathway could be a potential therapeutic strategy for the treatment of heart failure.

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Gene Transfer of Heat-Shock Protein 70 Reduces Infarct Size In Vivo After Ischemia/Reperfusion in the Rabbit Heart

Cited by 120 publications

References 46 publications

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway

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