Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients

Hirano, Tsutomu; Kashiwazaki, Kouichi; Moritomo, Yasunori; Nagano, Seishi; Adachi, Mitsuru

doi:10.1016/s0168-8227(97)01384-3

Cited by 53 publications

(33 citation statements)

References 30 publications

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“…Plasma level of HSPA1A is increased in patients with albuminuria (Morteza et al 2013b). In accordance, increased plasma level of PAI-1 was reported both in patients with diabetes (Hirano et al 1997) and patients with albuminuria (Stehouwer et al 2002). These observations imply a mechanistic link between HSP1A1 and PAI-1 in patients with diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 76%

“…Atherosclerosis is an inflammatory disease and is not merely the accumulation of lipids within the artery wall (Ross 1999). Increased plasma level of plasminogen activator inhibitor-1 (PAI-1) (Hirano et al 1997;Stehouwer et al 2002) and dysfunctional high-density lipoprotein (HDL) molecules (Navab et al 2009) are contributing factors and may be the results of this localized inflammation.…”

Section: Introductionmentioning

confidence: 99%

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The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

Nargesi

Shalchi

Nargesi

et al. 2016

Cell Stress and Chaperones

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We aimed to study the relation between plasma levels of stress-induced heat shock protein 70 (HSPA1A) with plasminogen activator inhibitor-1 (PAI-1) and highdensity lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and HDL-C/Apo-A1 ratio. In a matched case-control study on patients with diabetes (40 patients with albuminuria and 40 without albuminuria matched for age, sex, and body mass index), we observed that plasma levels of HSPA1A and PAI-1 are increased in patients with albuminuria (0.55±0.02 vs. 0.77±0.04 ng/ml, p value <0.001 for HSPA1A; 25.9±2 vs. 31.8±2.4 ng/ml, p value <0.05 for PAI-1). There was a significant correlation between HSPA1A and PAI-1 in diabetic patients without albuminuria (r=0.28; p value=0.04), but not in those with albuminuria (r=0.07; p value=0.63). No association was found between HSPA1A and HDL-C, between HSPA1A and Apo-A1, or between HSPA1A and HDL-C/Apo-A1 ratio. We concluded that there is a direct correlation between plasma HSPA1A and PAI-1 levels in patients with diabetes, which is lost when they develop albuminuria.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

Nargesi

Shalchi

Nargesi

et al. 2016

Cell Stress and Chaperones

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show abstract

“…Although less is known about the role of PAI-1 in the renal complications of diabetes, progression of diabetic nephropathy is possibly associated with PAI-1 production and activity [1,2]. In patients with diabetes, albuminuria is associated with increased plasma PAI-1 levels [23,24]. Intrarenal PAI-1 levels are increased in glomeruli and the interstitium, and PAI-1 is prominent in fibrotic areas and vessels in diabetic nephropathy [4,5].…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator inhibitor-1 production is pathogenetic in experimental murine diabetic renal disease

et al. 2007

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Aims/hypothesis Plasminogen activator inhibitor-1 (PAI-1, also known as serpin peptidase inhibitor, clade E [nexin, plasminogen activator inhibitor type 1], member 1 [SERPINE1]) plays a pathogenetic role in renal fibrosis. It is upregulated in experimental and human diabetic nephropathy. These studies assessed the effect of PAI-1 deficiency and overproduction on renal disease in experimental diabetes. Materials and methods Diabetes was induced by injection of streptozotocin in 6-week-old PAI-1-deficient mice, transgenic mice overexpressing Pai-1 and control mice.Animals were killed after 24 weeks of diabetes or after observation alone. Results Pai-1 mRNA was upregulated in kidneys from genetically normal mice with diabetes and in non-diabetic Pai-1 transgenic mice. PAI-1 was not further increased in kidneys from Pai-1 transgenic mice with diabetes. Diabetes-associated albuminuria and glomerular injury, as well as renal α-smooth muscle actin production, were ameliorated in diabetic PAI-1-deficient mice, an amelioration associated with attenuated increases in renal matrix metallopeptidase-2 expression and activity. Diabetic Pai-1 transgenic mice did not develop increased albuminuria or glomerular injury, but the tubulointerstitial area was modestly enhanced. In addition to the findings in diabetic mice, abnormalities also developed in 30-week-old PAI-1-deficient and Pai-1 transgenic mice without diabetes. PAI-1 deficiency resulted in increased tubulointerstitial area, TGFB1 protein and α-smooth muscle actin. Non-diabetic 30-week-old Pai-1 transgenic mice developed similar renal abnormalities and increased matrix metallopeptidase-2 activity, together with a modest increase in serum glucose and HbA 1c . Conclusions/interpretation These results demonstrate that endogenous PAI-1 deficiency protects mice from glomerular injury in longer term diabetes and that endogenous PAI-1 maintains normal renal interstitial structure in ageing not associated with diabetes.

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“…In particular, several authors have demonstrated that TGF-β, a profibrotic cytokine and potent stimulator of myofibroblast differentiation, is elevated in patients with diabetes and that it functions as a crucial factor in the progression of diabetic nephropathy [13,14]. Levels of plasminogen activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF), both key mediators of profibrotic TGF-β activity, are also significantly increased in tissue and plasma of experimental and human diabetic nephropathy [15][16][17][18][19][20]. Furthermore, Korpinen et al have demonstrated increased secretion of TGF-β by 2-day cultured peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes and showed an association of these TGF-β levels with the occurrence of diabetic nephropathy [21].…”

mentioning

confidence: 99%

Myofibroblast progenitor cells are increased in number in patients with type 1 diabetes and express less bone morphogenetic protein 6: a novel clue to adverse tissue remodelling?

et al. 2006

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Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients

Cited by 53 publications

References 30 publications

The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

Plasminogen activator inhibitor-1 production is pathogenetic in experimental murine diabetic renal disease

Myofibroblast progenitor cells are increased in number in patients with type 1 diabetes and express less bone morphogenetic protein 6: a novel clue to adverse tissue remodelling?

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