Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction: Figure 1

Santini, Daniele; Abbate, Antonio; Scarpa, Susanna; Vasaturo, Fortunata; Biondi‐Zoccai, Giuseppe; Bussani, Rossana; De-Giorgio, Fabio; Bassan, Fabio; Camilot, Debora; Marino, Mario; Feroce, Florinda; Baldi, Feliciano; Silvestri, Furio; Crea, Filippo; Baldi, Alfonso

doi:10.1136/jcp.2004.018986

Cited by 46 publications

(39 citation statements)

References 14 publications

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“…In spontaneously hypertensive rats, myocardial survivin expression is inversely correlated with apoptosis (Abbate et al, 2005). In patients with acute myocardial infarction, survivin expression in the non-infarcted myocardium is inversely associated with the occurrence of dilated cardiopathy and apoptosis (Santini et al, 2004). In the present study, we demonstrated that survivin RNAi increased cardiomyocyte apoptosis whereas survivin overexpression prevented DEPV-induced cardiomyocyte apoptosis.…”

Section: Discussionsupporting

confidence: 52%

“…A low level of survivin expression has been observed in normally differentiated tissues (Ambrosini et al, 1997). Interestingly, increased myocardial survivin expression has been reported to be associated with reduced infarct size and reduced apoptosis of the cardiomyocytes (Abbate et al, 2005;Fukuda et al, 2004;Santini et al, 2004). However, whether survivin can inhibit apoptosis of cardiomyocytes remains to be investigated.…”

Section: Introductionmentioning

confidence: 97%

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Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Yao

Wang

Cai

et al. 2007

Journal of Cell Science

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Survivin is known to be essential for cell division and to inhibit apoptosis during embryonic development and in adult cancerous tissues. However, the cardiovascular role of survivin is unknown. We observed that in cardiomyocytes cultured under conditions of serum and glucose deprivation (DEPV), the levels of survivin, Bcl-2 and extracellular signal-regulated kinase (ERK) were positively correlated with the anti-apoptotic action of a δ-opioid receptor agonist, [D-Ala2, D-Leu5]-enkephalin acetate (DADLE). By contrast, Bax translocation, mitochondrial membrane damage and reactive oxygen species (ROS) production were inversely correlated with the changes of survivin and Bcl-2. The use of RNA interference (RNAi) targeting survivin increased DEPV-induced cardiomyocyte apoptosis, whereas the anti-apoptotic effect of DADLE was blunted by survivin RNAi. Moreover, survivin transfection and overexpression provided protection against DEPV-induced cardiomyocyte apoptosis. Inhibition of ERK prevented the DADLE-induced decrease in apoptosis and Bax translocation, and increase in survivin and Bcl-2. DADLE-induced increase in survivin was also blunted by phosphoinositol 3-kinase (PI 3-kinase) inhibition. In conclusion, the present study provides the first direct evidence of an anti-apoptotic role of survivin mediating the anti-apoptotic effect of δ-opioid receptor activation in cardiomyocytes. ERK and PI 3-kinase were found to be upstream regulators of survivin. Mitochondrial membranes as well as ROS, Bcl-2 and Bax were also involved in this anti-apoptotic action.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 97%

Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Yao

Wang

Cai

et al. 2007

Journal of Cell Science

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“…Ischemia has been reported to up-regulate survivin expression in brain and heart. 41,42 However, in kidney we did not observe recruitment of further structures displaying survivin expression under hypoxia ( Figure 6B) or segmental infarction ( Figure 6, C and D). Two subtle differences were noted.…”

Section: Org)mentioning

confidence: 91%

The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells

Lechler

Bernhardt

et al. 2007

The American Journal of Pathology

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The inhibitor of apoptosis protein survivin is of critical importance for regulation of cellular division and survival. Published data point to a restricted function of survivin in embryonic development and cancer; thus survivin has been broadly proposed as an ideal molecular target for specific anti-cancer therapy. In contrast to this paradigm, we report here broad expression of survivin in adult differentiated tissues, as demonstrated at the mRNA and protein levels. Focusing on the kidney, survivin is strongly expressed in proximal tubuli, particularly at the apical membrane, which can be verified in rat, mouse, and human kidneys. In the latter, survivin expression seems to be even stronger in proximal tubuli than in adjacent cancerous tissue. Primary and immortalized human renal tubular cells also showed high levels of survivin protein expression, and RNA interference resulted in a partial G 2 /M arrest of the cell cycle and increased rate of apoptosis. In conclusion, survivin may be of importance for renal pathophysiology and pathology The kidney is an organ with a multitude of highly specific tasks, such as maintenance of water and electrolyte homeostasis, blood pressure control, and regulation of erythropoiesis. For most of these, the tubular system is of crucial importance. Renal tubular cells are very sensitive to a large number of clinically relevant stresses, such as hypoxia/ischemia, sepsis, or different toxic agents. The uniform pathomorphological appearance of such lesions is acute tubular necrosis, which leads to acute renal failure and has profound socio-economical impact, as well as high relevance for mortality of the critically ill patients. In addition, acute tubular injury can contribute to the progression of chronic kidney disease. 1Together with the thick ascending limb of Henle, the proximal tubule is the most sensitive region of the tubular system. Most of the transepithelial transport takes place in the proximal tubule, leading to a very high rate of energy consumption. At the same time the availability of energy substrates is restricted, because tubular cells are not able to perform glycolysis and the peritubular blood supply is easily hampered because of its postcapillary character.2,3 Taken together, the proximal tubule is a functionally important but highly susceptible structure. Considering the delicate nature of the proximal tubulus, its extraordinary ability for repair is remarkable, which involves a high rate of proliferation and differentiation processes potentially leading to complete restoration of

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“…11 Survivin is also detectable in nonproliferating, terminally differentiated tissues such as the myocardium, where it is induced in aged and failing hearts of spontaneously hypertensive rats 12 and upregulated after myocardial infarction in humans. 13 However, the biological function of survivin in the heart is unknown. By generating cardiomyocyte-specific survivin-deficient mice, we provide evidence that survivin controls cardiomyocyte proliferation and ploidy and that its loss leads to progressive heart failure through a reduction in total cardiomyocyte numbers.…”

mentioning

confidence: 99%

Survivin Determines Cardiac Function by Controlling Total Cardiomyocyte Number

et al. 2008

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Background-Survivin inhibits apoptosis and regulates cell division in many organs, but its function in the heart is unknown. Methods and Results-We show that cardiac-specific deletion of survivin resulted in premature cardiac death. The underlying cause was a dramatic reduction in total cardiomyocyte numbers as determined by a stereological method for quantification of cells per organ. The resulting increased hemodynamic load per cell led to progressive heart failure as assessed by echocardiography, magnetic resonance imaging, positron emission tomography, and invasive catheterization. The reduction in total cardiomyocyte number in ␣-myosin heavy chain (MHC)-survivin Ϫ/Ϫ mice was due to an Ϸ50% lower mitotic rate without increased apoptosis. This occurred at the expense of DNA accumulation because survivin-deficient cardiomyocytes displayed marked DNA polyploidy indicative of consecutive rounds of DNA replication without cell division. Survivin small interfering RNA knockdown in neonatal rat cardiomyocytes also led to polyploidization and cell cycle arrest without apoptosis. Adenoviral overexpression of survivin in cardiomyocytes inhibited doxorubicin-induced apoptosis, induced DNA synthesis, and promoted cell cycle progression. The phenotype of the ␣MHC-survivin Ϫ/Ϫ mice also allowed us to determine the minimum cardiomyocyte number sufficient for normal cardiac function. In human cardiomyopathy, survivin was potently induced in the failing heart and downregulated again after hemodynamic support by a left ventricular assist device. Its expression positively correlated with the mean cardiomyocyte DNA content. Conclusions-We suggest that the ontogenetically determined cardiomyocyte number may be an independent factor in the susceptibility to cardiac diseases. Through its profound impact on both cardiomyocyte replication and apoptosis, survivin may emerge as a promising new target for myocardial regeneration.

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Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction: Figure 1

Cited by 46 publications

References 14 publications

Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells

Survivin Determines Cardiac Function by Controlling Total Cardiomyocyte Number

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