Does cognition improve following LVAD implantation?

Pavol, Marykay; Willey, Joshua Z.; Wei, Ying Hui; Yuzefpolskaya, M.; Marshall, Randolph S.; Marascalco, Philip J.; Harwood, Jason; Lazar, Ronald M.

doi:10.1007/s11748-018-0947-5

Cited by 9 publications

(3 citation statements)

References 26 publications

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“…Increasing evidence suggest that decreased brain blood flow, increased reactive oxygen species (ROS) production and proinflammatory mechanisms accelerate the progression of neurodegenerative diseases such as vascular contributions to cognitive impairment and dementia (VCID) and patients with systemic inflammatory disease that are at risk for Alzheimer's disease (AD) and related dementias (Pullicino et al, 2008;Santos et al, 2013Santos et al, , 2017Corriveau et al, 2016;Gorelick et al, 2017;Pavol et al, 2018;Price et al, 2018). In older adults, heart failure (HF) results in decreased brain perfusion, and increased brain and systemic inflammation is known to increase the risk for the development of cognitive impairment and AD (Qiu et al, 2006;Cermakova et al, 2015;Love and Miners, 2016;Miners et al, 2016;Suzuki et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction

Hay

Polt

Heien

et al. 2019

J Pharmacol Exp Ther

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Increasing evidence indicates that decreased brain blood flow, increased reactive oxygen species (ROS) production, and proinflammatory mechanisms accelerate neurodegenerative disease progression such as that seen in vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease and related dementias. There is a critical clinical need for safe and effective therapies for the treatment and prevention of cognitive impairment known to occur in patients with VCID and chronic inflammatory diseases such as heart failure (HF), hypertension, and diabetes. This study used our mouse model of VCID/HF to test our novel glycosylated angiotensin-(1-7) peptide Ang-1-6-O-Ser-Glc-NH2 (PNA5) as a therapy to treat VCID and to investigate circulating inflammatory biomarkers that may be involved. We demonstrate that PNA5 has greater brain penetration compared with the native angiotensin-(1-7) peptide. Moreover, after treatment with 1.0/mg/kg, s.c., for 21 days, PNA5 exhibits up to 10 days of sustained cognitive protective effects in our VCID/HF mice that last beyond the peptide half-life. PNA5 reversed object recognition impairment in VCID/HF mice and rescued spatial memory impairment. PNA5 activation of the Mas receptor results in a dose-dependent inhibition of ROS in human endothelial cells. Last, PNA5 treatment decreased VCID/HF-induced activation of brain microglia/macrophages and inhibited circulating tumor necrosis factor a, interleukin (IL)-7, and granulocyte cell-stimulating factor serum levels while increasing that of the anti-inflammatory cytokine IL-10. These results suggest that PNA5 is an excellent candidate and "first-inclass" therapy for treating VCID and other inflammation-related brain diseases.

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Section: Introductionmentioning

confidence: 99%

A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction

Hay

Polt

Heien

et al. 2019

J Pharmacol Exp Ther

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“…По результатам исследования не было обнаружено различий в показателях когнитивной функции между исходными показателями и через 1 месяц после имплантации LVAD, но отмечалось значительное улучшение когнитивной функции через 3 месяца наблюдения. Полученные результаты свидетельствуют о том, что при отсутствии послеоперационного инсульта у некоторых пациентов могут наблюдаться когнитивные улучшения через 3 месяца после установки LVAD, даже если нет признаков улучшения при 30-дневном обследовании [44].…”

Section: потенциальные новые терапевтические возможности лечения хсн ...unclassified

Cognitive impairment in chronic heart failure. How new therapeutic options for the treatment of chronic heart failure affect cognitive function?

Aksenova,

Osmolovskaya,

Petrukhina

et al. 2024

Evrazijskij kardiologičeskij žurnal

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Heart failure is a serious chronic illness and a global healthcare problem. Patients with heart failure have increased hospital readmission rates and mortality around the world. Heart failure often coexists with comorbidities of which cognitive impairment is particularly important. Сognitive impairment is present in around 30% to 80% in heart failure decreases quality of life and increases the frequency of repeated hospitalizations, increases mortality and worsens the prognosis in such patients. Despite existing research, the underlying pathophysiology of the relationship between heart failure and cognitive impairment remains poorly understood. The article discusses the best available evidence concerning different pathophysiological mechanisms behind cognitive impairment in individuals with heart failure. Heart failure and cognitive impairment have a number of common pathophysiological pathways including reduced cerebral blood flow, inflammation, neurohumoral activations, oxidative stress and changes in serum biomarkers or proteins. Understanding the pathophysiology of diseases will allow the effective evaluation of health status and development of suitable treatments. Prompt detection of cognitive impairment will bring about better clinical outcomes in heart failure patients. This review raises questions about the relationship between heart failure and cognitive dysfunction, provides evidence on the impact of new therapeutic options for treating heart failure on cognitive function, and suggests potential future research directions. For example, implantation of an artificial left ventricle may improve cognitive function; however, there are studies on immediate improvement in cognitive function followed by gradual deterioration over time after implantation of an artificial left ventricle, which requires long-term study In addition, evidence is provided for the effectiveness of using a relaxation scenario in virtual reality technology to reduce anxiety and affective complaints in somatic hospitalized patients, but the ability to improve cognitive function in patients with chronic heart failure remains to be explored.

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“…Recent scientific research indicates that the progression of many neurodegenerative diseases results from vascular influences that contribute to cognitive impairment and dementia (VCID). Alzheimer's disease and related dementia result from decreased brain blood flow, increased production of reactive oxygen species (ROS), and proinflammatory mechanisms (Pavol et al, 2018). Hay et al (Hay et al, 2019) tested their novel glycosylated Ang-(1-7) peptide Ang-1-6-O-Ser-Glc-NH2 (PNA5) as a therapy to treat VCID on a mouse model of VCID and heart failure (HF) (VCID/HF).…”

Section: Structurally Modified Homologs Of Ang-(1-7)mentioning

confidence: 99%

Targeting the Protective Arm of the Renin-Angiotensin System: Focused on Angiotensin-(1–7)

Khajehpour

Aghazadeh‐Habashi

2021

J Pharmacol Exp Ther

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The in vivo application and efficacy of many therapeutic peptides is limited due to their instability and proteolytic degradation. Novel strategies for developing therapeutic peptides with higher stability toward proteolytic degradation would be extremely valuable. Such approaches could improve systemic bioavailability and enhance therapeutic effects. The renin-angiotensin system (RAS) is a hormonal system within the body essential for the regulation of blood pressure and fluid balance. The RAS is composed of two opposing classical and protective arms. The balance between these two arms is critical for the homeostasis of the body's physiological function. Activation of the RAS results in the suppression of its protective arm that has been reported in inflammatory and pathological conditions such as arthritis, cardiovascular diseases, diabetes, and cancer. Clinical application of the Angiotensin-(1-7) (Ang-(1-7)), a RAS critical regulatory peptide, augments the protective arm and restores balance hampered by its enzymatic and chemical instability. Several attempts to increase the half-life and efficacy of this heptapeptide using more stable analogs and different drug delivery approaches have been made. This review article provides an overview of efforts targeting the RAS protective arm. It provides a critical analysis of Ang-(1-7) or its homologs' novel drug delivery systems using different administration routes, their pharmacological characterization, and therapeutic potential in various clinical settings.Significance Statement: Ang-(1-7) is a unique peptide component of the RAS system with vast potential for clinical applications that modulate various inflammatory diseases. Novel Ang-(1-7) peptide drug delivery could compensate its lack of stability for effective clinical application.

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Does cognition improve following LVAD implantation?

Cited by 9 publications

References 26 publications

A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction

A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction

Cognitive impairment in chronic heart failure. How new therapeutic options for the treatment of chronic heart failure affect cognitive function?

Targeting the Protective Arm of the Renin-Angiotensin System: Focused on Angiotensin-(1–7)

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