A Review of Sirt1 and Sirt1 Modulators in Cardiovascular and Metabolic Diseases

Pillarisetti, Sivaram

doi:10.2174/157489008786263989

Cited by 105 publications

(89 citation statements)

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“…The inducible Sirt1 Ϫ/Ϫ mice used in our studies may mimic some of the responses to PM 2.5 exposure in aging. [21][22][23][24][25][26] Our study suggests that decreased Sirt1 expression in the elderly could be a potential risk factor for PM-induced coagulation and inflammation.…”

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 68%

“…[21][22][23][24][25][26] NF-B, a transcription factor that regulates inflammatory responses, is an endogenous substrate for Sirt1. [27][28][29][30] It has been reported that Sirt1 deacetylates NF-B, thereby inhibiting its activity in several in vitro and in vivo systems.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23][24][25][26] Interestingly, Sirt1 expression in the lung is reduced in the elderly who are known to be particularly susceptible to PM-induced cardiopulmonary mortality. 24,33 In this study, we investigated the role of Sirt1 in PM-induced lung coagulation.…”

Section: Introductionmentioning

confidence: 99%

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Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, controls lung inflammation and coagulation after PM exposure. Sirt1 knock-out mice exhibited aggravated lung vascular leakage and inflammation after PM exposure, which was correlated with increased NF-B acetylation and activation. Furthermore, Sirt1 knock-out mice were highly susceptible to PM-induced lung coagulation as demonstrated by increased fibrin formation. The increased fibrin formation was associated with reduced tissue factor pathway inhibitor (TFPI) expression and increased plasminogen activator inhibitor-1 (PAI-1) activity in the lungs, thus favoring elevated coagulation and disrupted fibrinolysis responses. Thrombomodulin (TM), a central player of the anticoagulant protein C system, is regulated by Kruppel-like factor 2 (KLF2) at the transcriptional level. IntroductionExposure to ambient particulate matter (PM) air pollution has been associated with impaired pulmonary function and increased cardiovascular disease-related mortality including inflammation and thrombosis. 1-5 Acute exposure to increased ambient fine particulate matter Ͻ 2.5 m in diameter (PM 2.5 ) was estimated to cause the premature deaths of tens of thousands of people each year in the United States. 6 Urban particulate matter (UPM) PM 2.5, one of the major air pollutants closely monitored by the US Environmental Protection Agency (EPA), is a complex mixture of substances that are directly emitted into the air from dust, soot, smoke, and combustion. 6 To protect public health, the EPA issued the current 24-hour PM 2.5 standard at 35 g/m 3 . 6 Despite the enormous health problems caused by PM 2.5 exposure, there have been few studies performed to explore the molecular mechanisms of PM 2.5 -induced lung vascular dysfunction. PM 2.5 can reach deep in the lung to the small airway and alveoli, 6 and directly cause lung inflammation and injury. [7][8][9][10][11][12][13] The pulmonary complications may lead to detrimental effects on other organs, particularly cardiovascular dysfunction such as systemic microvascular dysfunction and thrombosis. 1,2,4,5,13 A recent study demonstrated that short-term UPM exposure triggered the activation of primary hemostasis in healthy mice, with no substantial secondary hemostasis activation, leading to arterial but not venous thrombosis. 5 Whereas another study showed that short-term UPM exposure may cause activation of coagulation responses and fibrin formation in the lung. 14 Tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1) play important roles in coagulation and fibrinolysis cascades, respectively. TFPI is an inhibitor of tissue factor (TF)-mediated coagulation responses. 15 PAI-1, on the other hand, is a major regulator of fibrinolysis, which functions by in...

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Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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“…Several studies point to Sirt1 as a chief regulator of NO synthesis in endothelium (Milne et al 2007;Pillarisetti 2008;Potente et al 2007) employing an Akt-mediated pathway of eNOS phosphorylation (Lovren et al 2009) or promoting eNOS catalytic activity through deacetylation of lysines 496 and 506 (Mattagajasingh et al 2007). As NO itself appears to reciprocally activate Sirt1 expression and activity (Ota et al 2007), then Sirt1-eNOS axis emerges as a decisive regulatory mechanism in CC endothelium.…”

Section: Discussionmentioning

confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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“…During chronic pressure overload such as in chronic hypertension, PGC1α gene controls fatty acid oxidation and Tfam gene increases number of mitochondria are downregulated which is consistant with the fact that mitochondrial respiratory function is reduced during end-stage heart failure [32].…”

Section: Discussionmentioning

confidence: 99%

Induction of Sirt1 and PGC1α Signalling Pathway in Cardiac Mitochondrial Biogenesis by Aspirin

Kamble¹,

Kulkarni²

2018

Eur J Exp Bio

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Aims: We hypothesized that acetyl salicylic acid (Aspirin, ASA) treament has ability to induce Sirtuin 1, 4 (Sirt1 and Sirt4) and it downstream targets, peroxisome proliferatoractivated receptor-gamma co-activator-1α (PGC1α) and mitochondrial transcription factor A (Tfam) gene in cultured HL1 cardiomyocytes. We also assume that hydrogen peroxide (H 2 O 2 ) formed during redox reactions is inducer of Sirt1 gene. Methods and Results:Atrial Cardiomyocyts HL1 cells were cultured in Claycomb medium with 10% FBS, 100μmol/L norepinephrine, and 4 mmol/L L-glutamine (Invitrogen, Carlsbad, CA) in gelatin coated flasks. Cells were maintained at 37°C in an atmosphere containing 5% CO 2 . Cells were then incubated with either 50 μM and 0.25 mM ASA for 48 h in the same medium. Respective controls were maintained with alcohol alone. At the end of the treatment, the medium was removed and the cells were washed with PBS and harvested in Trizol® for isolation of RNA. RT-PCR was performed for the analysis of gene expression. Our results in cultured HL1 cardiomyocytes showed ASA treament induced Sirt1 and Sirt4 genes via H 2 O 2 generation. Increase in Sirt1 gene activated PGC1α and Tfam gene. ASA have also induced antioxidant enzymes, glutathione peroxidase (GPX) and catalase (CAT) gene. Conclusion:We conclude from our results that ASA is a potential anti-atherosclerotic drug and an increase in Sirt1 gene further suggest that it can induce anti-inflammatory action. It can also interfere with Nfkb signaling pathway that can prevent foam cell formation. However, specific overexpression of PGC1α and Tfam gene in HL1 cardiomyocyte can increase mitochondrial biogenesis and prevent the development of heart failure.

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A Review of Sirt1 and Sirt1 Modulators in Cardiovascular and Metabolic Diseases

Cited by 105 publications

References 0 publications

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Induction of Sirt1 and PGC1α Signalling Pathway in Cardiac Mitochondrial Biogenesis by Aspirin

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