The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function

Shityakov, Sergey; Nagai, Michiaki; Ergün, Süleyman; Braunger, Barbara M.; Förster, Carola

doi:10.3390/biom12081113

Cited by 13 publications

(3 citation statements)

References 200 publications

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“…According to several reports, DR reflects diastolic cardiac abnormality, a sign of HF. Hence, DR could be regarded as part of the progression of disease eventually leading to macrovascular damage and HF [ 50 ].…”

Section: Association Of Dr With Other Diabetes-related Complicationsmentioning

confidence: 99%

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

et al. 2023

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Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A “domino effect” is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

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Section: Association Of Dr With Other Diabetes-related Complicationsmentioning

confidence: 99%

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

et al. 2023

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“…In the cardiovascular system, and like many other vital organs, the heart is susceptible to the effects of aging. Inflammation is a hallmark of aging and other coexisting comorbidities linked to age-related decline, such as heart failure, cardiovascular disease, neurodegeneration, vascular dementia, and Alzheimer’s disease, but also age-related hearing loss, age-related macular degeneration, and type 2 diabetes [ 28 , 72 , 73 , 74 ]. Inflammation is also associated with TTS.…”

Section: Discussionmentioning

confidence: 99%

Blood Biomarkers in Takotsubo Syndrome Point to an Emerging Role for Inflammaging in Endothelial Pathophysiology

et al. 2023

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Takotsubo syndrome (TTS), an acute cardiac condition characterized by transient wall motion abnormalities mostly of the left ventricle, results in difficulties in diagnosing patients. We set out to present a detailed blood analysis of TTS patients analyzing novel markers to understand the development of TTS. Significant differences in proinflammatory cytokine expression patterns and sex steroid and glucocorticoid receptor (GR) expression levels were observed in the TTS patient collected. Remarkably, the measured catecholamine serum concentrations determined from TTS patient blood could be shown to be two orders of magnitude lower than the levels determined from experimentally induced TTS in laboratory animals. Consequently, the exposure of endothelial cells and cardiomyocytes in vitro to such catecholamine concentrations did not damage the cellular integrity or function of either endothelial cells forming the blood–brain barrier, endothelial cells derived from myocardium, or cardiomyocytes in vitro. Computational analysis was able to link the identified blood markers, specifically, the proinflammatory cytokines and glucocorticoid receptor GR to microRNA (miR) relevant in the ontogeny of TTS (miR-15) and inflammation (miR-21, miR-146a), respectively. Amongst the well-described risk factors of TTS (older age, female sex), inflammaging-related pathways were identified to add to these relevant risk factors or prediagnostic markers of TTS.

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“…Inflammation is a hallmark of aging, and other coexisting comorbidities linked to age-related decline, such as heart failure, cardiovascular disease, neurodegeneration, vascular dementia and Alzheimer's disease but also age-related hearing loss, age-related macular degeneration and type 2 diabetes. 24,69,70,71 Inflammation is also associated with TTS. Recently, a novel portemanteau of inflammation and aging has been coined, "inflammaging", which is defined as chronic, low-grade inflammation accumulated and worsening over age, presumably contributing to the pathogenesis of various age-related pathologies.…”

Section: Bioinformatic Extrapolation: Tts -An Inflammaging Disorder?mentioning

confidence: 99%

Blood biomarkers in Takotsubo syndrome point to an emerging role for inflammaging in disease pathophysiology

Nagai¹,

Shityakov²,

Smetak

et al. 2023

Preprint

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Takotsubo syndrome (TTS), an acute cardiac condition characterized by transient wall motion abnormalities mostly of the left ventricle, results in difficulties in diagnosing patients. We set out to present a detailed blood analysis of TTS patients analyzing novel markers to understand the development of TTS. Significant differences in pro-inflammatory cytokine expression patterns, sex steroid and glucocorticoid receptor (GR) expression levels were observed in the TTS patient collective. Remarkably, the measured catecholamine serum concentrations determined from TTS patient blood could be shown to be two orders of magnitude lower than the levels determined from experimentally induced TTS in laboratory animals. Consequently, exposure of endothelial cells and cardiomyocytes in vitro to such catecholamine concentrations did not damage the cellular integrity or function of neither endothelial cells forming the blood brain barrier, endothelial cells derived from myocardium nor cardiomyocytes in vitro. Computational analysis was able to link the identified blood markers, specifically, the pro-inflammatory cytokines and glucocorticoid receptor GR to microRNA (miR) relevant in the ontogeny of TTS (miR-15), and inflammation (miR-21, miR-146a), respectively. Amongst the well-described risk factors of TTS (older age, female gender), inflammaging-related pathways were identified to add to these relevant risk factors or prediagnostic markers of TTS.

show abstract

The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function

Cited by 13 publications

References 200 publications

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

Blood Biomarkers in Takotsubo Syndrome Point to an Emerging Role for Inflammaging in Endothelial Pathophysiology

Blood biomarkers in Takotsubo syndrome point to an emerging role for inflammaging in disease pathophysiology

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