Increased ACE and Decreased ACE2 Expression in Kidneys from Patients with IgA Nephropathy

Mizuiri, Sonoo; Hemmi, Hiromichi; Arita, Michitsune; Aoki, Toshiyuki; Ohashi, Yasushi; Miyagi, Moriatsu; Sakai, Ken; Shibuya, Kazutoshi; Hase, Hiroki; Aikawa, Atsushi

doi:10.1159/000319648

Cited by 34 publications

(35 citation statements)

References 57 publications

(32 reference statements)

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“…This is consistent with the findings in animal models of hypertension [32], although renal ACE2 expression and activity is unaltered during established hypertension in adult SHR-SP and TGR(mREN2)27 rats [33]. Furthermore, it is reported that ACE2 staining is decreased and ACE staining is increased in glomeruli in adult IgAN patients [34]. These results are different from the findings of the present study.…”

Section: Discussionsupporting

confidence: 82%

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Urushihara¹,

Seki²,

Tayama³

et al. 2013

Am J Nephrol

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Background: Angiotensin-converting enzyme (ACE) 2 is a homolog of ACE and is thought to be a potent counter-regulator against ACE activity. However, the role of ACE2 has not been investigated in pediatric patients with IgA nephropathy (IgAN). This study was performed to examine the relationship between ACE2 expression and the development of pediatric IgAN. Methods: We performed immunohistochemical analysis of ACE2 and ACE in 39 patients with pediatric IgAN and 14 patients with minor glomerular abnormalities, and elucidated the effects of various cytokines on ACE2 expression in cultured human mesangial cells. Results: ACE2 expression levels in glomeruli and tubules were positively correlated with the mesangial hypercellularity score, while ACE expression levels in glomeruli and tubules are not. Multiple regression analysis showed that the mesangial hypercellularity score correlated with the ACE2 expression level in glomeruli and the urinary protein-creatinine ratio. In IgAN patients not treated with a renin-angiotensin system blocker, ACE2 expression levels in glomeruli were significantly increased compared to patients with minor glomerular abnormalities. IgAN patients treated with a renin-angiotensin system blocker did not show this increase in ACE2 expression. Furthermore, cultured human MC showed increased ACE2 mRNA and protein after treatment with IL-1β, a pro-inflammatory cytokine in IgAN. In fact, glomerular expressions of IL-1β were remarkably increased in patients with IgAN. Conclusion: These data indicate that ACE2 expression in glomeruli is associated with mesangial hypercellularity in early lesions of pediatric IgAN.

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Section: Discussionsupporting

confidence: 82%

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Urushihara¹,

Seki²,

Tayama³

et al. 2013

Am J Nephrol

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“…Sensitive indicators of ROS production, lipid peroxidation products and the glomerulosclerosis score were markedly enhanced in those mice while ARB prevented these increases, which strongly supports the notion that ACE2 plays a role in Ang II-induced glomerular injury. More recently, a similar relationship between ACE2 and ACE expression in diseased glomeruli was reported even in patients with IgAN [43]. …”

Section: Involvement Of the Glomerular Ras In Disease Progressionsupporting

confidence: 66%

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Kubo

2011

Clin Exp Nephrol

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Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease.

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“…Increased salt intake and related kidney damage were associated with reduced cortical expression of ACE2 in obese Zucker rats (69) and increased ACE/ACE2 mRNA and protein ratio in glomeruli of uninephrectomized WKY (70), respectively. The similar ratio between ACE and ACE2 was also found in renal biopsies from patients with hypertension when compared to subjects with normal blood pressure (71) as well as in patients with IgA nephropathy (72) and diabetes (57;73). No differences in ACE2 expression between patients with focal segmental glomerulosclerosis and control cohort has been reported (73); these data suggested that decrease in ACE2 is not a general response to kidney injury.…”

Section: Renoprotective Role Of Ace2supporting

confidence: 64%

ACE2: Angiotensin II/Angiotensin-(1–7) Balance in Cardiac and Renal Injury

et al. 2014

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Our current recognition of the renin-angiotensin system is more convoluted than originally thought due to the discovery of multiple novel enzymes, peptides, and receptors inherent to this interactive biochemical cascade. Over the last decade angiotensin converting enzyme 2 (ACE2) has emerged as a key player in the pathophysiology of hypertension and cardiovascular and renal disease due to its pivotal role in metabolizing vasoconstrictive/hypertrophic/proliferative angiotensin II into favorable angiotensin-(1-7). This review addresses a considerable advancement in research on the role of tissue ACE2 in development and progression of hypertension and cardiorenal injury. We also summarize the results from recent clinical and experimental studies suggesting that serum or urine soluble ACE2 may serve as a novel biomarker or independent risk factor relevant for diagnosis and prognosis of cardiorenal disease. Recent proceedings on novel therapeutic approaches to enhance ACE2/angiotensin-(1-7) axis are also reviewed.

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Increased ACE and Decreased ACE2 Expression in Kidneys from Patients with IgA Nephropathy

Cited by 34 publications

References 57 publications

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

ACE2: Angiotensin II/Angiotensin-(1–7) Balance in Cardiac and Renal Injury

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