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  1. Book ; Online ; E-Book: Studies on atherosclerosis

    Rodriguez-Porcel, Martin / Chade, Alejandro R. / Miller, Jordan D.

    (Oxidative stress in applied basic research and clinical practice)

    2017  

    Author's details Martin Rodriguez-Porcel, Alejandro R. Chade, Jordan D. Miller editors
    Series title Oxidative stress in applied basic research and clinical practice
    Keywords Life sciences ; Cardiology ; Nephrology ; Oxidative stress
    Subject code 571.9453
    Language English
    Size 1 Online-Ressource (xv, 138 Seiten), Diagramme
    Publisher Humana Press
    Publishing place New York
    Publishing country United States
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT019485079
    ISBN 978-1-4899-7693-2 ; 9781489976918 ; 1-4899-7693-0 ; 1489976914
    DOI 10.1007/978-1-4899-7693-2
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Novel Drug Delivery Technologies and Targets for Renal Disease.

    Chade, Alejandro R / Bidwell, Gene L

    Hypertension (Dallas, Tex. : 1979)

    2022  Volume 79, Issue 9, Page(s) 1937–1948

    Abstract: The burden of acute and chronic kidney diseases to the health care system is exacerbated by the high mortality that this disease carries paired with the still limited availability of comprehensive therapies. A reason partially resides in the complexity ... ...

    Abstract The burden of acute and chronic kidney diseases to the health care system is exacerbated by the high mortality that this disease carries paired with the still limited availability of comprehensive therapies. A reason partially resides in the complexity of the kidney, with multiple potential target cell types and a complex structural environment that complicate strategies to protect and recover renal function after injury. Management of both acute and chronic renal disease, irrespective of the cause, are mainly focused on supportive treatments and renal replacement strategies when needed. Emerging preclinical evidence supports the feasibility of drug delivery technology for the kidney, and recent studies have contributed to building a robust catalog of peptides, proteins, nanoparticles, liposomes, extracellular vesicles, and other carriers that may be fused to therapeutic peptides, proteins, nucleic acids, or small molecule drugs. These fusions can display a precise renal uptake, an enhanced circulating time, and a directed intraorgan biodistribution while protecting their cargo to improve therapeutic efficacy. However, several hurdles that slow the transition towards clinical applications are still in the way, such as solubility, toxicity, and sub-optimal renal targeting. This review will discuss the feasibility and current limitations of drug delivery technologies for the treatment of renal disease, offering an update on their potential and the future directions of these promising strategies.
    MeSH term(s) Drug Delivery Systems ; Humans ; Kidney Diseases/drug therapy ; Liposomes/chemistry ; Nanoparticles ; Technology ; Tissue Distribution
    Chemical Substances Liposomes
    Language English
    Publishing date 2022-06-02
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.122.17944
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cardiac epigenetic changes in VEGF signaling genes associate with myocardial microvascular rarefaction in experimental chronic kidney disease.

    Eirin, Alfonso / Chade, Alejandro R

    American journal of physiology. Heart and circulatory physiology

    2022  Volume 324, Issue 1, Page(s) H14–H25

    Abstract: Chronic kidney disease (CKD) is common in patients with heart failure and often results in left ventricular diastolic dysfunction (LVDD). However, the mechanisms responsible for cardiac damage in CKD-LVDD remain to be elucidated. Epigenetic alterations ... ...

    Abstract Chronic kidney disease (CKD) is common in patients with heart failure and often results in left ventricular diastolic dysfunction (LVDD). However, the mechanisms responsible for cardiac damage in CKD-LVDD remain to be elucidated. Epigenetic alterations may impose long-lasting effects on cellular transcription and function, but their exact role in CKD-LVDD is unknown. We investigate whether changes in cardiac site-specific DNA methylation profiles might be implicated in cardiac abnormalities in CKD-LVDD. CKD-LVDD and normal control pigs (
    MeSH term(s) Swine ; Animals ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Microvascular Rarefaction/complications ; Microvascular Rarefaction/genetics ; 5-Methylcytosine ; Ventricular Dysfunction, Left ; Renal Insufficiency, Chronic/genetics ; Epigenesis, Genetic ; Heart Failure/genetics ; Heart Failure/complications ; RNA, Messenger
    Chemical Substances Vascular Endothelial Growth Factor A ; 5-Methylcytosine (6R795CQT4H) ; RNA, Messenger
    Language English
    Publishing date 2022-11-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00522.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cardiac micro-RNA and transcriptomic profile of a novel swine model of chronic kidney disease and left ventricular diastolic dysfunction.

    Chade, Alejandro R / Eirin, Alfonso

    American journal of physiology. Heart and circulatory physiology

    2022  Volume 323, Issue 4, Page(s) H659–H669

    Abstract: Chronic kidney disease (CKD) is an independent risk factor for the development of heart failure, but the underlying mechanisms remain unknown. Using a novel translational swine model of CKD and cardiac dysfunction, we hypothesize that CKD alters the ... ...

    Abstract Chronic kidney disease (CKD) is an independent risk factor for the development of heart failure, but the underlying mechanisms remain unknown. Using a novel translational swine model of CKD and cardiac dysfunction, we hypothesize that CKD alters the cardiac miRNA and transcriptomic profile that associate with cardiac remodeling and metabolic processes implicated in the development of left ventricular diastolic dysfunction (CKD-LVDD). CKD-LVDD and normal control pigs (
    MeSH term(s) Adenosine Triphosphate ; Animals ; Diastole/physiology ; Fatty Acids ; Lipids ; MicroRNAs/genetics ; RNA, Messenger/genetics ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/genetics ; Swine ; Transcriptome ; Ventricular Dysfunction, Left/etiology ; Ventricular Remodeling/genetics
    Chemical Substances Fatty Acids ; Lipids ; MicroRNAs ; RNA, Messenger ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2022-08-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00333.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Kidney Intrinsic Mechanisms as Novel Targets in Renovascular Hypertension.

    Eirin, Alfonso / Chade, Alejandro R / Lerman, Lilach O

    Hypertension (Dallas, Tex. : 1979)

    2023  Volume 81, Issue 2, Page(s) 206–217

    Abstract: Almost a hundred years have passed since obstruction of the renal artery has been recognized to raise blood pressure. By now chronic renovascular disease (RVD) due to renal artery stenosis is recognized as a major source of renovascular hypertension and ... ...

    Abstract Almost a hundred years have passed since obstruction of the renal artery has been recognized to raise blood pressure. By now chronic renovascular disease (RVD) due to renal artery stenosis is recognized as a major source of renovascular hypertension and renal disease. In some patients, RVD unaccompanied by noteworthy renal dysfunction or blood pressure elevation may be incidentally identified during peripheral angiography. Nevertheless, in others, RVD might present as a progressive disease associated with diffuse atherosclerosis, leading to loss of renal function, renovascular hypertension, hemodynamic compromise, and a magnified risk for cardiovascular morbidity and mortality. Atherosclerotic RVD leads to renal atrophy, inflammation, and hypoxia but represents a potentially treatable cause of chronic renal failure because until severe fibrosis sets in the ischemic kidney, it retains a robust potential for vascular and tubular regeneration. This remarkable recovery capacity of the kidney begs for early diagnosis and treatment. However, accumulating evidence from both animal studies and randomized clinical trials has convincingly established the inadequate efficacy of renal artery revascularization to fully restore renal function or blood pressure control and has illuminated the potential of therapies targeted to the ischemic renal parenchyma to instigate renal regeneration. Some of the injurious mechanisms identified as potential therapeutic targets included oxidative stress, microvascular disease, inflammation, mitochondrial injury, and cellular senescence. This review recapitulates the intrinsic mechanisms that orchestrate renal damage and recovery in RVD and can be harnessed to introduce remedial opportunities.
    MeSH term(s) Animals ; Humans ; Hypertension, Renovascular/diagnosis ; Hypertension, Renovascular/etiology ; Hypertension, Renovascular/drug therapy ; Kidney ; Renal Artery Obstruction ; Kidney Function Tests ; Atherosclerosis ; Chronic Disease ; Inflammation
    Language English
    Publishing date 2023-10-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.123.21362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1488: Show issues Location:
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  6. Article ; Online: Understanding and managing atherosclerotic renovascular disease: still a work in progress.

    Chade, Alejandro R

    F1000Research

    2018  Volume 7

    Abstract: Atherosclerotic renovascular disease (ARVD) is an unresolved therapeutic dilemma despite extensive pre-clinical and clinical studies. The pathophysiology of the disease has been widely studied, and many factors that may be involved in progressive renal ... ...

    Abstract Atherosclerotic renovascular disease (ARVD) is an unresolved therapeutic dilemma despite extensive pre-clinical and clinical studies. The pathophysiology of the disease has been widely studied, and many factors that may be involved in progressive renal injury and cardiovascular risk associated with ARVD have been identified. However, therapies and clinical trials have focused largely on attempts to resolve renal artery stenosis without considering the potential need to treat the renal parenchyma beyond the obstruction. The results of these trials show a staggering consistence: although nearly 100% of the patients undergoing renal angioplasty show a resolution of the vascular obstruction, they do not achieve significant improvements in renal function or blood pressure control compared with those patients receiving medical treatment alone. It seems that we may need to take a step back and reconsider the pathophysiology of the disease in order to develop more effective therapeutic strategies. This mini-review discusses potential therapeutic alternatives that focus on the renal parenchyma distal to the vascular obstruction and may provide additional tools to enhance current treatment of ARVD.
    MeSH term(s) Angioplasty ; Animals ; Atherosclerosis/pathology ; Atherosclerosis/therapy ; Disease Management ; Humans ; Hypertension, Renovascular/complications ; Parenchymal Tissue/drug effects ; Renal Artery Obstruction/pathology ; Renal Artery Obstruction/therapy
    Language English
    Publishing date 2018-11-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402 ; 2046-1402
    ISSN (online) 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.16369.1
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  7. Article ; Online: Expanding landscape of coronary microvascular disease in co-morbid conditions: Metabolic disease and beyond.

    McCallinhart, Patricia E / Chade, Alejandro R / Bender, Shawn B / Trask, Aaron J

    Journal of molecular and cellular cardiology

    2024  

    Abstract: Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that ... ...

    Abstract Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that CMD is an independent predictor of cardiac morbidity and mortality in patients with obesity and metabolic disease. CMD is comprised of functional, structural, and mechanical impairments that synergize and ultimately reduce coronary blood flow in metabolic disease and in other co-morbid conditions, including transplant, autoimmune disorders, chemotherapy-induced cardiotoxicity, and remote injury-induced CMD. This review summarizes the contemporary state-of-the-field related to CMD in metabolic and these other co-morbid conditions based on mechanistic data derived mostly from preclinical small- and large-animal models in light of available clinical evidence and given the limitations of studying these mechanisms in humans. In addition, we also discuss gaps in current understanding, emerging areas of interest, and opportunities for future investigations in this field.
    Language English
    Publishing date 2024-05-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80157-4
    ISSN 1095-8584 ; 0022-2828
    ISSN (online) 1095-8584
    ISSN 0022-2828
    DOI 10.1016/j.yjmcc.2024.05.004
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  8. Article ; Online: Small Vessels, Big Role: Renal Microcirculation and Progression of Renal Injury.

    Chade, Alejandro R

    Hypertension (Dallas, Tex. : 1979)

    2017  Volume 69, Issue 4, Page(s) 551–563

    MeSH term(s) Awards and Prizes ; Disease Progression ; Humans ; Kidney/blood supply ; Kidney/pathology ; Microcirculation/physiology ; Renal Circulation/physiology ; Renal Insufficiency, Chronic/pathology
    Language English
    Publishing date 2017-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.116.08319
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Renal mitochondrial injury in the pathogenesis of CKD: mtDNA and mitomiRs.

    Irazabal, Maria V / Chade, Alejandro R / Eirin, Alfonso

    Clinical science (London, England : 1979)

    2022  Volume 136, Issue 5, Page(s) 345–360

    Abstract: Chronic kidney disease (CKD) is a public health concern that affects over 200 million people worldwide and is associated with a tremendous economic burden. Therefore, deciphering the mechanisms underpinning CKD is crucial to decelerate its progression ... ...

    Abstract Chronic kidney disease (CKD) is a public health concern that affects over 200 million people worldwide and is associated with a tremendous economic burden. Therefore, deciphering the mechanisms underpinning CKD is crucial to decelerate its progression towards end-stage renal disease (ESRD). Renal tubular cells are populated with a high number of mitochondria, which produce cellular energy and modulate several important cellular processes, including generation of reactive oxygen species (ROS), calcium homeostasis, proliferation, and apoptosis. Over the past few years, increasing evidence has implicated renal mitochondrial damage in the pathogenesis of common etiologies of CKD, such as diabetes, hypertension, metabolic syndrome (MetS), chronic renal ischemia, and polycystic kidney disease (PKD). However, most compelling evidence is based on preclinical studies because renal biopsies are not routinely performed in many patients with CKD. Previous studies have shown that urinary mitochondrial DNA (mtDNA) copy numbers may serve as non-invasive biomarkers of renal mitochondrial dysfunction. Emerging data also suggest that CKD is associated with altered expression of mitochondria-related microRNAs (mitomiRs), which localize in mitochondria and regulate the expression of mtDNA and nucleus-encoded mitochondrial genes. This review summarizes relevant evidence regarding the involvement of renal mitochondrial injury and dysfunction in frequent forms of CKD. We further provide an overview of non-invasive biomarkers and potential mechanisms of renal mitochondrial damage, especially focusing on mtDNA and mitomiRs.
    MeSH term(s) Biomarkers/metabolism ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Female ; Humans ; Kidney/metabolism ; Male ; Mitochondria/metabolism ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/metabolism
    Chemical Substances Biomarkers ; DNA, Mitochondrial
    Language English
    Publishing date 2022-03-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20210512
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  10. Article ; Online: A Boolean Model of Microvascular Rarefaction to Predict Treatment Outcomes in Renal Disease.

    Williams, Erika / Chade, Alejandro R

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 440

    Abstract: Despite advances in renovascular disease (RVD) research, gaps remain between experimental and clinical outcomes, translation of results, and the understanding of pathophysiological mechanisms. A predictive tool to indicate support (or lack of) for ... ...

    Abstract Despite advances in renovascular disease (RVD) research, gaps remain between experimental and clinical outcomes, translation of results, and the understanding of pathophysiological mechanisms. A predictive tool to indicate support (or lack of) for biological findings may aid clinical translation of therapies. We created a Boolean model of RVD and hypothesized that it would predict outcomes observed in our previous studies using a translational swine model of RVD. Our studies have focused on developing treatments to halt renal microvascular (MV) rarefaction in RVD, a major feature of renal injury. A network topology of 20 factors involved in renal MV rarefaction that allowed simulation of 5 previously tested treatments was created. Each factor was assigned a function based upon its interactions with other variables and assumed to be "on" or "off". Simulations of interventions were performed until outcomes reached a steady state and analyzed to determine pathological processes that were activated, inactivated, or unchanged vs. RVD with no intervention. Boolean simulations mimicked the results of our previous studies, confirming the importance of MV integrity on treatment outcomes in RVD. Furthermore, our study supports the potential application of a mathematical tool to predict therapeutic feasibility, which may guide the design of future studies for RVD.
    MeSH term(s) Animals ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Kidney Diseases/metabolism ; Kidney Diseases/therapy ; Microvascular Rarefaction/metabolism ; Microvascular Rarefaction/therapy ; Models, Statistical ; Swine ; Treatment Outcome ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Antioxidants ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2020-01-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-57386-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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