Tu-P7:246 Protective role of HSP27 in atherosclerosis

Martin-Ventura, José Luis; Nicolas, Valérie; Houard, Xavier; Blanco-Colio, L.M.; Leclercq, Agnès; Egido, J.; Vranckx, Roger; Michel, Jean Baptiste; Meilhac, Olivier

doi:10.1016/s1567-5688(06)80950-5

Cited by 2 publications

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“…Thereby, the protein enrichment increased species diversity by revealing HSP27 isoforms with different molecular weights or isoelectric point features that could not be detected in native extracts and thus qualified as of low abundance. Previous studies have reported that HSP27 can be present in different proteolytic fragments [37] and phosphorylated forms [38][39][40][41] or oligomers [42]. Moreover, increased HSP27 proteolysis in atherosclerotic plaques has also been reported in a secretome study [37].…”

Section: The Specific Case Of Hsp27 Species Expressionmentioning

confidence: 67%

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

et al. 2012

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Atherosclerosis is one of the most important causes of cardiovascular and cerebrovascular events. Although phenotypic differentiation between stable and unstable plaques is currently possible, proteomic analysis of the atherosclerotic plaque could offer a global view of the atherosclerosis pathology. With the objective to highlight the detection of low-abundance proteins, we reduced the dynamic range of proteins by combinatorial peptide ligand library treatment of human carotid artery atherosclerotic plaques. After enrichment step, abundance of major proteins was decreased, revealing different protein profiles as assessed by both SDS-polyacrylamide gel electrophoresis and two-dimensional electrophoresis comparative analyses. Identification of proteins that were contained in a spot allowed finding large differences between noncomplicated and complicated plaques from carotid atherosclerotic lesions. Novel low-abundance proteins were detected correlating very well with biological alterations related to atherosclerosis (heat shock protein 27 (HSP27) isoforms, aldehyde dehydrogenase, moesin, Protein kinase C delta-binding protein, and inter-α trypsin inhibitor family heavy chain-related protein (ITIH4)). At the same time, the differential expression of known proteins of interest such as hemoglobin β-chain and heat shock protein 27 between noncomplicated and hemorrhagic complicated plaques was maintained after enrichment step. The detection of different isoforms of a low-abundance protein such as heat shock protein 27 species was actually improved after enrichment of tissue protein extracts. All of these findings clearly support further investigations in view to confirm the role of these proteins as possible biomarkers.

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Section: The Specific Case Of Hsp27 Species Expressionmentioning

confidence: 67%

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

et al. 2012

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“…Similarly, overexpression of heat shock protein 27 (Hsp27) protects cisplatininduced apoptosis of mouse fibroblasts (39) and human ovarian tumor cells (40). Interestingly, plasma Hsp27 levels were decreased in atherosclerotic patients compared with healthy subjects (41), and down-regulation of this protein decreases VSMC resistance to proteolytically induced apoptosis (42). We chose to further investigate PP1c␥1, because it was the most common cDNA expressed in VSMC resistant to DMNQ and because inhibitors of PP1c␥1 are proapoptotic (18,19), indicating a potential role for PP1c␥1 in protecting against apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Protective Role for Protein Phosphatase 1cγ1 against Oxidative Stress-induced Vascular Smooth Muscle Cell Apoptosis

Tchivilev¹,

Madamanchi²,

Vendrov

et al. 2008

Journal of Biological Chemistry

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The development of therapeutic strategies to inhibit reactive oxygen species (ROS)-mediated damage in blood vessels has been limited by a lack of specific targets for intervention. Targeting ROS-mediated events in the vessel wall is of interest, because ROS play important roles throughout atherogenesis. In early atherosclerosis, ROS stimulate vascular smooth muscle cell (VSMC) growth, whereas in late stages of lesion development, ROS induce VSMC apoptosis, causing atherosclerotic plaque instability. To identify putative protective genes against oxidative stress, mouse aortic VSMC were infected with a retroviral human heart cDNA expression library, and apoptosis was induced in virus-infected cells by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) treatment. A total of 17 different, complete cDNAs were identified from the DMNQ-resistant VSMC clones by PCR amplification and sequencing. The cDNA encoding PP1c␥1 (catalytic subunit of protein phosphatase 1) was present in several independent DMNQ-resistant VSMC clones. DMNQ increased mitochondrial ROS production, caspase-3/7 activity, DNA fragmentation, and decreased mitochondrial transmembrane potential in VSMC while decreasing PP1c␥1 activity and expression. Depletion of PP1c␥1 expression by short hairpin RNA significantly enhanced basal as well as DMNQ-induced VSMC apoptosis. PP1c␥1 overexpression abrogated DMNQ-induced JNK1 activity, p53 Ser 15 phosphorylation, and Bax expression and protected VSMC against DMNQ-induced apoptosis. In addition, PP1c␥1 overexpression attenuated DMNQ-induced caspase-3/7 activation and DNA fragmentation. Inhibition of p53 protein expression using small interfering RNA abrogated DMNQ-induced Bax expression and significantly attenuated VSMC apoptosis. Together, these data indicate that PP1c␥1 overexpression promotes VSMC survival by interfering with JNK1 and p53 phosphorylation cascades involved in apoptosis.Enhanced reactive oxygen species (ROS) 3 generation plays an important role in the proliferation, migration, or apoptosis of vascular smooth muscle cells (VSMC), all of which have been implicated in the pathophysiology of vascular diseases, including atherosclerosis. VSMC proliferation and migration are important in the development of atherosclerotic lesions, and VSMC apoptosis is a histologic hallmark of advanced atherosclerosis (1). Additionally, human VSMC isolated from coronary plaques are more susceptible to apoptosis than VSMC isolated from normal arteries (2). Apoptosis of VSMC in atherosclerotic plaques is accompanied by numerous other events that increase the likelihood of plaque rupture. These include decreases in collagen and extracellular matrix protein production, decreased fibrous cap thickness, accumulation of macrophages along the shoulder of the plaque, and increases in the size of the necrotic core and amount of cellular debris within the plaque (3). A better understanding of the mechanisms that regulate VSMC apoptosis could lead to the development of strategies to stabilize atherosclerotic plaques.Identifying genes that c...

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Tu-P7:246 Protective role of HSP27 in atherosclerosis

Cited by 2 publications

References 0 publications

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

Identification of a Protective Role for Protein Phosphatase 1cγ1 against Oxidative Stress-induced Vascular Smooth Muscle Cell Apoptosis

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