Matrix metalloproteinase −2, −9 and arterial stiffness in children and adolescents: The role of chronic kidney disease, diabetes, and hypertension

Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.

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Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria

Clinical Science ◽

10.1042/cs20150517 ◽

2016 ◽

Vol 130 (7) ◽

pp. 525-538 ◽

Cited By ~ 26

Author(s):

Helena Pulido-Olmo ◽

Concha F. García-Prieto ◽

Gloria Álvarez-Llamas ◽

María G. Barderas ◽

Fernando Vivanco ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Metalloproteinase 9

Resistant albuminuria developed under chronic RAS blockade is strongly associated with increased circulating MMP-9 activity mediated by oxidative stress.

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The Association between Nitric Oxide Pathway, Blood Pressure Abnormalities, and Cardiovascular Risk Profile in Pediatric Chronic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20215301 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5301 ◽

Cited By ~ 6

Author(s):

Hsu ◽

Lu ◽

Lo ◽

Lin ◽

Tain

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Arterial Stiffness ◽

Children And Adolescents ◽

Young Patients ◽

Left Ventricular ◽

Stiffness Index ◽

Lv Mass

Cardiovascular disease (CVD) is common in chronic kidney disease (CKD), while major CV events are rare in young CKD patients. In addition to nitric oxide (NO)-related biomarkers, several surrogate markers have been assessed to stratify CV risk in youth with CKD, including 24-h ambulatory blood pressure monitoring (ABPM), carotid artery intima-media thickness (cIMT), pulse wave velocity (PWV), ABPM-derived arterial stiffness index (AASI), flow-mediated dilatation (FMD), and left ventricular mass index (LVMI). The aim of this study was to identify subclinical CVD through the analysis of indices of CV risk in children and adolescents with CKD. Between 2016 and 2018, the prospective observational study enrolled 125 patients aged 3 to 18 years with G1–G4 CKD stages. Close to two-thirds of young patients with CKD exhibited blood pressure (BP) abnormalities on ABPM. CKD children with abnormal office BP showed lower plasma arginine levels and arginine-to-asymmetric dimethylarginine (ADMA) ratio, but higher ratios of ADMA-to-symmetric dimethylarginine (SDMA) and citrulline-to-arginine. High PWV and AASI, indices of arterial stiffness, both strongly correlated with high BP load. Additionally, LV mass and LVMI exhibited strong correlations with high BP load. Using an adjusted regression model, we observed the citrulline-to-arginine ratio was associated with 24-h systolic and diastolic BP, systolic blood pressure (SBP) load, and diastolic blood pressure (DBP) load. Early assessments of NO-related parameters, BP load abnormalities, arterial stiffness indices, and LV mass will aid in early preventative care toward decreasing CV risk later in life for children and adolescents with CKD.

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The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease

Kidney Research and Clinical Practice ◽

10.23876/j.krcp.2018.37.3.222 ◽

2018 ◽

Vol 37 (3) ◽

pp. 222-229 ◽

Cited By ~ 3

Author(s):

Harin Rhee ◽

Miyeun Han ◽

Sang Soo Kim ◽

Il Young Kim ◽

Hye Won Lee ◽

...

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Matrix Metalloproteinase ◽

Mouse Models ◽

Matrix Metalloproteinase 2 ◽

Aged Mouse

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Chronic kidney disease and cardiovascular events: a focus on central blood pressure

Systemic Hypertension ◽

10.26442/sg29181 ◽

2017 ◽

Vol 14 (1) ◽

pp. 58-60

Author(s):

I T Murkamilov ◽

K A Aitbaev ◽

I S Sabirov ◽

V V Fomin ◽

F A Yusupov

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Arterial Stiffness ◽

Renal Dysfunction ◽

Cardiovascular Events ◽

Vascular Complications ◽

Vascular Wall ◽

Cardio Vascular

The purpose of the review - to present the literature on the role of central arterial pressure (CAP) and arterial stiffness progression cardio-vascular complications (CVC) and renal dysfunction in patients with chronic kidney disease (CKD). The main provisions. In this review we discuss the pathogenetic questions damaging effect of increasing CAP and arterial stiffness on the vascular wall, the development of arteriosclerosis, atherosclerosis and destabilization of atherosclerotic plaque in the blood vessels of the kidneys. All this is the direct cause of the CVC and renal dysfunction in CKD.

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