Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-α expression, and apoptotic death in failing human myocardium

D'Ascia, C; Cittadini, Antonio; Monti, Maria Gaia; Riccio, Giuseppe; Saccà, Luigi

doi:10.1093/eurheartj/ehi579

Cited by 75 publications

(67 citation statements)

References 27 publications

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“…19 Recent data from D'Ascia et al demonstrated that myocardial tissue from patients revealed a significant decrease in TNF-␣ expression with increased capillary density after 6 months of cardiac resynchronization therapy. 36 Moreover, endotoxemia tended to decrease intestinal functional capillary density, whereas it elevated TNF-␣ and interleukin levels in rats. 37 It is suggested that an increase in capillary density is not followed by an increase in inflammatory responses.…”

Section: Et Al Effect Of Temporal Pretreatment With Arb On Stroke mentioning

confidence: 95%

Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density

Mogi

Iwanami

et al. 2008

Stroke

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Background and Purpose-We investigated the effect of temporary treatment with a nonhypotensive dose of valsartan on ischemic brain damage in C57BL/6 mice. Methods-We separated the mice into 3 groups of valsartan treatment before middle cerebral artery (MCA) occlusion: (1) for 4 weeks: Val (2W, 2W); (2) for 2 weeks followed by its cessation for 2 weeks: Val (2W, -); and (3) no treatment for 4 weeks: Val (-, -). Results-Ischemic volume, DNA damage, superoxide production, and mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-␣ on the ipsilateral side after 24 hours of MCA occlusion were significantly reduced in both Val (2W, 2W) and Val (2W, -) mice compared with those in Val (-, -) mice, whereas these parameters were larger in Val (2W, -) mice than in Val (2W, 2W) mice. Moreover, mice in both the Val (2W, 2W) and Val (2W, -) groups exhibited an increase in cerebral blood flow in the peripheral territory of the MCA 1 hour after MCA occlusion, with increases in endothelial nitric oxide synthase activation and nitric oxide production. Before MCA occlusion, treatment with valsartan did not influence superoxide production or mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-␣ in the brain. However, the capillary density in the brain in both Val (2W, 2W) and Val (2W, -) mice was increased before MCA occlusion. Conclusions-Our results suggest that temporary valsartan treatment could protect against ischemic brain damage even after its cessation, at least in part due to an increase in capillary density.

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Section: Et Al Effect Of Temporal Pretreatment With Arb On Stroke mentioning

confidence: 95%

Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density

Mogi

Iwanami

et al. 2008

Stroke

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“…However, recent studies by our and other laboratories have revealed many changes at the cellular and molecular levels as well, and these present a unique profile for CRT unmatched by other HF treatments to date. For example, marked heterogeneity of regional gene expression is reversed (10), the cytoprotective Akt pathway is stimulated and is coupled with reduced apoptosis (11,12), calcium handling and associated ultrastructure of the sarcoplasmic reticulum improve (13)(14)(15), mitochondrial efficiency and ATP synthase activity are enhanced via a redox switch (16), ion channel function regulating the action potential is improved (17,18), and resting as well as β-adrenergicstimulated myocyte function are markedly restored by a mechanism involving regulators of G protein signaling (19,20). Interestingly, while CRT substantially improves resting myocyte function throughout the ventricle, this is not consistently matched by increases in the calcium transient (17,20), suggesting CRT may also enhance myofilament responses to calcium.…”

Section: Introductionmentioning

confidence: 99%

Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β

Kirk¹,

Holewinski²,

Kooij³

et al. 2013

J. Clin. Invest.

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Cardiac resynchronization therapy (CRT), the application of biventricular stimulation to correct discoordinate contraction, is the only heart failure treatment that enhances acute and chronic systolic function, increases cardiac work, and reduces mortality. Resting myocyte function also increases after CRT despite only modest improvement in calcium transients, suggesting that CRT may enhance myofilament calcium responsiveness. To test this hypothesis, we examined adult dogs subjected to tachypacing-induced heart failure for 6 weeks, concurrent with ventricular dyssynchrony (HF dys ) or CRT. Myofilament force-calcium relationships were measured in skinned trabeculae and/or myocytes. Compared with control, maximal calcium-activated force and calcium sensitivity declined globally in HF dys ; however, CRT restored both. Phosphatase PP1 induced calcium desensitization in control and CRT-treated cells, while HF dys cells were unaffected, implying that CRT enhances myofilament phosphorylation. Proteomics revealed phosphorylation sites on Z-disk and M-band proteins, which were predicted to be targets of glycogen synthase kinase-3β (GSK-3β). We found that GSK-3β was deactivated in HF dys and reactivated by CRT. Mass spectrometry of myofilament proteins from HF dys animals incubated with GSK-3β confirmed GSK-3β-dependent phosphorylation at many of the same sites observed with CRT. GSK-3β restored calcium sensitivity in HF dys , but did not affect control or CRT cells. These data indicate that CRT improves calcium responsiveness of myofilaments following HF dys through GSK-3β reactivation, identifying a therapeutic approach to enhancing contractile function.

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“…CRT is also associated with decline in global apoptosis and enhanced cell-survival signaling [60,61]. Biventricular pacing reduces interstitial remodeling [61].…”

Section: Cardiac Resynchronization Therapy (Crt)mentioning

confidence: 99%

Role of New Therapies in Reducing Mortality and Major Morbidity in Patients with Systolic Heart Failure

Yurevich¹,

Borer²

2017

The Role of the Clinical Cardiac Electrophysiologist in the Management of Congestive Heart Failure

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Though heart failure therapies, particularly for systolic heart failure, have developed rapidly and markedly during the past four decades, a need for additional relief persists and is progressively being met. Two new drugs have been approved for marketing in the United States within the past two years, and two other glucose lowering therapies for diabetes appear to have efficacy for heart failure as well. In addition, device therapy for heart failure has progressed markedly during the past 5 years, particularly in refinements of the indications and applications of devices to minimize symptoms and hospitalizations and to maximize survival. This chapter will outline these recent developments.

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Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-α expression, and apoptotic death in failing human myocardium

Abstract: We provide the first evidence that CRT reduces interstitial remodelling, TNF-alpha expression, and apoptosis. The data may explain the beneficial effects of CRT on CHF progression and survival.

Cited by 75 publications

References 27 publications

Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density

Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density

Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β

Role of New Therapies in Reducing Mortality and Major Morbidity in Patients with Systolic Heart Failure

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