Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications

Jankauskas, Stanislovas S.; Gambardella, Jessica; Sardu, Celestino; Lombardi, Angela; Santulli, Gaetano

doi:10.3390/ncrna7030039

Cited by 44 publications

(34 citation statements)

References 178 publications

(216 reference statements)

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“…Hyperglycemia (HG) is common in patients suffering from cardiovascular diseases [17], is an established independent predictor of severe outcomes, even in absence of frank dia-betes mellitus (DM) [18,19], and has been proposed to exacerbate endothelial dysfunction in hypertensive subjects [20][21][22][23][24][25][26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

Mone

Gambardella

Pansini

et al. 2021

Cells

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Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study to assess the effects of high-glucose and metformin on brain microvascular endothelial cells (ECs) and on cognitive impairment in frail hypertensive patients. We tested the effects of metformin on high-glucose-induced cell death, cell permeability, and generation of reactive oxygen species in vitro, in human brain microvascular ECs. To investigate the consequences of hyperglycemia and metformin in the clinical scenario, we recruited frail hypertensive patients and we evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according to the glycemic status (normoglycemic vs. hyperglycemic) and the use of metformin. We enrolled 376 patients, of which 209 successfully completed the study. We observed a significant correlation between MoCA score and glycemia. We found that hyperglycemic patients treated with metformin had a significantly better MoCA score than hyperglycemic patients treated with insulin (18.32 ± 3.9 vs. 14.94 ± 3.8; p < 0.001). Our in vitro assays confirmed the beneficial effects of metformin on human brain microvascular ECs. To our knowledge, this is the first study correlating MoCA score and glycemia in frail and hypertensive older adults, showing that hyperglycemia aggravates cognitive impairment.

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Section: Introductionmentioning

confidence: 99%

Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

Mone

Gambardella

Pansini

et al. 2021

Cells

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“…The change of miRNA expression in T2DM patients has been established by many researchers, and their results revealed that miR-155 is crucial for insulin sensitivity regulation of liver, adipose tissue, and skeletal muscle. Moreover, a series of clinical researches have also found low miR-155 levels in the serum of patients with T2DM, which may lead to insulin resistance [ 48 ]. Meanwhile, increasing evidence has revealed that miRNAs are differentially expressed in sarcopenia of the elderly, plasma miR-155 level in the sarcopenia group was significantly reduced compared to the non-sarcopenia group [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus

2022

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Background Sarcopenia is characterized by the age-associated loss of skeletal muscle mass and strength that develops progressively and plays an important role in the disability of the elderly. It has received growing attention over the last decade and has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM). The existence of T2DM could increase the risk of developing sarcopenia through multiple mechanisms including advanced glycation end-product accumulation. Meanwhile, sarcopenia would alter glucose disposal and may contribute to the development and progression of T2DM due to reduced muscle mass. Methods We implemented transcriptomic analysis of skeletal muscle biopsy specimens in sarcopenia patients and proliferating myoblasts or differentiated myotubes from individuals with T2DM. Related microarray data were selected from Gene Expression Omnibus (GEO) to screen the genes, which were differentially expressed for sarcopenia and T2DM. Multiple combinatorial statistical methods and bioinformatics tools were used to analyze the common DEGs. Meanwhile, functional enrichment analysis was also carried out. Furthermore, we constructed the protein-protein interaction (PPI), as well as transcription factor (TF)-gene interactions network and TF-miRNA coregulatory network. Finally, based on the common DEGs, drug compounds were speculated using the Drug Signatures database (DSigDB). Results A total of 1765 and 2155 DEGs of sarcopenia and T2DM were screened, respectively. 15 common genes (LXN, CIB2, PEA15, KANK2, FGD1, NMRK1, PLCB1, SEMA4G, ADARB1, UPF3A, CSTB, COL3A1, CD99, ETV3, FJX1) correlated with sarcopenia and T2DM simultaneously were then identified, and 3 genes (UPF3A, CSTB and PEA15) of them were regarded as hub genes. Functional enrichment analysis revealed several shared pathways between two diseases. In addition, according to the TF-gene interactions network and TF-miRNA coregulatory network, part of TF and miRNA may be identified as key regulator in sarcopenia and T2DM at the same time (e.g., CREM and miR-155). Notably, drug compounds for T2DM and sarcopenia were also suggested, such as coenzyme Q10. Conclusion This study revealed that sarcopenia and T2DM may share similar pathogenesis and provided new biological targets and ideas for early diagnosis and effective treatment of sarcopenia and T2DM.

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“…Of note, miRs could be over-expressed in high-risk patients also at the level of organs not directly involved in atherosclerotic processes, such as the peripheral adipose tissue [35,36]. In this setting, the adipose tissue could work as an active gland in the synthesis and relapse of miRs that negatively influence cardiac performance and atherosclerotic processes.…”

Section: Discussionmentioning

confidence: 99%

“…Consistently, the expected clinical benefit in patients with an acute ischemic event would be the introduction of specific medical treatment, which either would modify the expression of miRs resulting in better risk factor control or reduction in atherosclerotic burden, or specific miRs inhibitors to modify target miRs expression [13,35]. In line, in obese pre-diabetics, metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27 were associated with reduction in left ventricle mass and intima-media thickness [36].…”

Section: Discussionmentioning

confidence: 99%

Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events

et al. 2021

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Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001–1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26–3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22–6.12) and PAD (HR = 3.47, 95%CI = 1.88–6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000–1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01–1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001–1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).

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Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications

Cited by 44 publications

References 178 publications

Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus

Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events

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