Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis

Kawajiri, Masakazu; Mogi, Masaki; Higaki, Naoyuki; Matsuoka, Takeshi; Ohyagi, Yasumasa; Tsukuda, Kana; Kohara, Katsuhiko; Horiuchi, Masatsugu; Miki, Tetsuro; Kira, Jun Ichi

doi:10.1177/1352458508097923

Cited by 58 publications

(47 citation statements)

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“…Increased levels of ACE2 and Ang-(1-7) were found in the cerebrospinal fluid of multiple sclerosis patients. 90 Moreover, Lu et al 91 showed that chronic central administration of Ang-(1-7) reduces the infarct area and provides cerebroprotection following focal cerebral ischemia/reperfusion in rats. The authors suggest that the heptapeptide modulates in vivo NO release and eNOS expression in this stroke model.…”

Section: Redox-sensitive Signaling By the Ace2-ang-(1-7)-mas Axismentioning

confidence: 99%

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

2010

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The renin-angiotensin-aldosterone system (RAAS) is a pivotal regulator of physiological homeostasis and diseases of the cardiovascular system. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas. This newly defined ACE2-angiotensin-(1-7)-Mas axis was shown to have a critical role in the vasculature and in the heart, exerting mainly protective effects. One important mechanism of the classic and the new RAAS regulate vascular function is through the regulation of redox signaling. Angiotensin II is a classic prooxidant peptide that increases superoxide production through the activation of NAD(P)H oxidases. This review summarizes the current knowledge about the ACE2-angiotensin-(1-7)-Mas axis and redox signaling in the context of cardiovascular regulation and disease. By interacting with its receptor Mas, angiotensin-(1-7) induces the release of nitric oxide from endothelial cells and thereby counteracts the effects of angiotensin II. ACE2 converts angiotensin II to angiotensin-(1-7) and, thus, is a pivotal regulator of the local effects of the RAAS on the vessel wall. Taken together, the ACE2-angiotensin-(1-7)-Mas axis emerges as a novel therapeutic target in the context of cardiovascular and metabolic diseases.

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Section: Redox-sensitive Signaling By the Ace2-ang-(1-7)-mas Axismentioning

confidence: 99%

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

2010

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“…In the chronic stage of MS, perivascular astrocytes are progressively lost [6], rendering the BBB leaky. The reduction of angiotensin II levels in the CSF that we observed may in part reflect such a process [3,7].…”

Section: Introductionmentioning

confidence: 67%

“…We previously reported an increase in the level of ACE and a decrease in the level of ACE2 in MS patients without anti-AQP4 antibody [7], and suggested a compensatory mechanism to be operative in response to a decrease in the level of angiotensin II, namely, up-regulation of the synthesizing enzyme (ACE) and downregulation of the catabolizing enzyme (ACE2). Although we could not reproduce the increase in ACE level in this series of MS patients, at least the ACE level was not decreased as compared with that in controls.…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin II, ACE and ACE2 concentrations in CSF were measured by established ELISA systems for angiotensin II (SPI-bio, Montigny-leBretonneux, France), ACE (R&D Systems, Minneapolis, MN), and ACE2 (AdipoGen Inc., Seoul, Korea), as described previously [3,7]. According to the manufacturer's data, the precision, recovery, and linearity of these assays are as follows: for the human angiotensin II ELISA, the intra-assay coefficients of variation (CVs) are 2.0-10.0%, inter-assay CVs are 5.0-15.0%, the recovery range is 80-115% and the linearity is around 90% of expected; for the human ACE ELISA, the intra-assay CVs are 3.4-4.0%, inter-assay CVs are 4.9-7.7%, the recovery range is 91-106% and linearity is around 105% of expected; for the human ACE2 ELISA, the intra-assay CVs are 5.3-9.9%, inter-assay CVs are 5.4-10.8%, the recovery range is 81-113%, and linearity is around 100% of expected.…”

Section: Measurement Of Angiotensin II Ace and Ace2 Concentrations Imentioning

confidence: 99%

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CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity

Matsushita

Isobe

Kawajiri

et al. 2010

Journal of the Neurological Sciences

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“…We demonstrated that cerebrospinal fluid levels of angiotensin and angiotensin-converting enzymes produced and secreted from astrocyte end feet were significantly decreased in NMO [148] and MS [149,150] patients, suggesting that injury to astrocyte end feet and dampening of astrocytic barrier functions may occur in both MS and NMO.…”

Section: Neuroprotective Aspectsmentioning

confidence: 93%

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

Kira

2016

Neuroimmunological Diseases

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Multiple sclerosis (MS) is a disease that targets myelin in the central nervous system (CNS). It is thought to be an autoimmune disease but this is not yet proven. Genome-wide association studies have revealed many susceptibility genes for MS, and the functions of these genes are mostly immune-related, supporting the autoimmune hypothesis. Increased numbers of T cells showing inter-and intramolecular epitope spreading against myelin proteins; increased cerebrospinal fluid (CSF) levels of interferon (IFN)-γ, interleukin (IL)-17, and downstream pro-inflammatory cytokines; exacerbation of disease following IFN-γ administration; and increased percentages of T helper (Th)1 cells secreting IFN-γ and of Th17 cells secreting IL-17 at relapse all support T-cell involvement in MS lesion formation. B-cell infiltration in the CNS parenchyma is not prominent, while B-cell follicles in the meninges appear to have a close correlation with subpial demyelination, suggesting an involvement of autoantibodies. However, no specific autoantibodies for MS have been detected, although anti-aquaporin-4 antibodies are a specific biomarker for neuromyelitis optica (NMO). We reported the extensive loss of connexins (Cxs) 43, 32, and 47 in acute lesions in patients with Baló's concentric sclerosis, MS, and NMO. Such loss of astroglial and oligodendroglial Cxs could induce widespread disruption of the glial syncytium, leading to failure of energy source transfer. Thus, loss of Cxs in acute MS lesions may contribute to extensive lesion formation. In the Japanese population, HLA-DRB1*0405 is the most common susceptibility allele for non-NMO MS. DRB1*0405 carriers comprise >40 % of all Japanese MS patients, and this proportion is higher in younger generations. HLA-DRB1*0405-positive MS patients show characteristic features, such as younger age at onset, fewer brain lesions, fewer CSF IgG abnormalities, and a slower progression. The recent increase in the number of MS patients in this subgroup may explain the overall decrease in onset age, as shown by the fourth nationwide survey of Japanese MS patients. Therefore, changes in environmental factors may have increased susceptibility to MS in Japanese populations with certain genetic backgrounds.

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Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis

Abstract: These results further indicate an alteration of the intrathecal renin-angiotensin system in patients with MS.

Cited by 58 publications

References 10 publications

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

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