MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease

Zietzer, Andreas; Steffen, Eva; Niepmann, Sven Thomas; Düsing, Philip; Hosen, Mohammed Rabiul; Liu, Weiyi; Jamme, Paul; Al‐Kassou, Baravan; Goody, Philip Roger; Zimmer, Sebastian; Reiners, Katrin S.; Pfeifer, Alexander; Böhm, Michael; Werner, Nikos; Nickenig, Georg; Jansen, Felix

doi:10.1093/cvr/cvaa322

Cited by 23 publications

(24 citation statements)

References 57 publications

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“…A number of upregulated miRNA in this study, including miR-130a-3p and miR-1825, target the TGFβ pathway [168]. Own data reveal that CKD patients exhibit significantly lower vesicular levels of vascular protective miR-126-3p and miR-130a-3p [169].…”

Section: Extracellular Vesicles As Intercellular Messengers In Ckd and Cadmentioning

confidence: 58%

“…In vitro treatment with the model uremia toxin IS leads to a decreased packaging of the two miRNAs into EV through a hnRNPU-dependent sorting mechanism. This altered miRNA packaging was shown to be functionally relevant as it influences endothelial cell migratory capacity [169]. Another miRNA, miR-92a, which is relevant for endothelial function circulates in augmented levels in the peripheral blood of CKD patients.…”

Section: Extracellular Vesicles As Intercellular Messengers In Ckd and Cadmentioning

confidence: 99%

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Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches

et al. 2021

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Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.

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Section: Extracellular Vesicles As Intercellular Messengers In Ckd and Cadmentioning

confidence: 58%

Section: Extracellular Vesicles As Intercellular Messengers In Ckd and Cadmentioning

confidence: 99%

Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches

et al. 2021

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“…With the levels of inflammation associated miR‐155 being highest at the site, the markedly elevated levels in COVID‐19 might be reflective of the since widely‐appreciated endothelialitis, which is COVID‐19‐specific 22 . In line with this, miR‐126, which is known to be protective from endothelial damage and deprived in chronic cardiovascular disease, 23 was decreased in our discovery cohort, albeit this finding was not reproducible in the validation cohort. Within the COVID‐19 group, the patients with higher miR‐208a and miR‐499 also had higher procalcitonin and lactate levels.…”

Section: Discussionmentioning

confidence: 71%

Circulating cardiovascular microRNAs in critically ill COVID‐19 patients

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Seeliger

Derda

et al. 2021

European J of Heart Fail

116

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Aims Coronavirus disease 2019 (COVID‐19) is a still growing pandemic, causing many deaths and socio‐economic damage. Elevated expression of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry receptor angiotensin‐converting enzyme 2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID‐19 or influenza‐associated acute respiratory distress syndrome (Influenza‐ARDS) admitted to the intensive care unit and healthy controls. Methods and results Circulating miRs (miR‐21, miR‐126, miR‐155, miR‐208a, and miR‐499) were analysed in a discovery cohort consisting of patients with mechanically‐ventilated COVID‐19 ( n = 18) and healthy controls ( n = 15). A validation study was performed in an independent cohort of mechanically‐ventilated COVID‐19 patients ( n = 20), Influenza‐ARDS patients ( n = 13) and healthy controls ( n = 32). In both cohorts, RNA was isolated from serum and cardiovascular disease/inflammatory‐relevant miR concentrations were measured by miR‐specific TaqMan PCR analyses. In both the discovery and the validation cohort, serum concentration of miR‐21, miR‐155, miR‐208a and miR‐499 were significantly increased in COVID‐19 patients compared to healthy controls. Calculating the area under the curve using receiver operating characteristic analysis miR‐155, miR‐208a and miR‐499 showed a clear distinction between COVID‐19 and Influenza‐ARDS patients. Conclusion In this exploratory study, inflammation and cardiac myocyte‐specific miRs were upregulated in critically ill COVID‐19 patients. Importantly, miR profiles were able to differentiate between severely ill, mechanically‐ventilated Influenza‐ARDS and COVID‐19 patients, indicating a rather specific response and cardiac involvement of COVID‐19.

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“…In contrast, CKD patients have decreased miR-126 levels, which is expressed in endothelial cells and has proangiogenic properties (Brigant et al, 2016;Fourdinier et al, 2019). Interestingly, low miR-130a-3p levels were found in microparticles isolated from endothelial cells exposed to IS, as well as from CKD and coronary artery disease patients (Zietzer et al, 2020). IS induced endothelial microparticles in vitro with increased levels of miR-181a-5p, miR-4454, and miR-150-5p, which may be related to modulation of the inflammation process (Carmona et al, 2017).…”

Section: Uremic Toxins In Endothelial Dysfunctionmentioning

confidence: 98%

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

et al. 2021

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The kidneys and heart share functions with the common goal of maintaining homeostasis. When kidney injury occurs, many compounds, the so-called “uremic retention solutes” or “uremic toxins,” accumulate in the circulation targeting other tissues. The accumulation of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and inorganic phosphate leads to a loss of a substantial number of body functions. Although the concept of uremic toxins is dated to the 1960s, the molecular mechanisms capable of leading to renal and cardiovascular injuries are not yet known. Besides, the greatest toxic effects appear to be induced by compounds that are difficult to remove by dialysis. Considering the close relationship between renal and cardiovascular functions, an understanding of the mechanisms involved in the production, clearance and overall impact of uremic toxins is extremely relevant for the understanding of pathologies of the cardiovascular system. Thus, the present study has as main focus to present an extensive review on the impact of uremic toxins in the cardiovascular system, bringing the state of the art on the subject as well as clinical implications related to patient’s therapy affected by chronic kidney disease, which represents high mortality of patients with cardiac comorbidities.

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MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease

Cited by 23 publications

References 57 publications

Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches

Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches

Circulating cardiovascular microRNAs in critically ill COVID‐19 patients

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

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