Angiotensin-Converting Enzyme 2 (ACE2) in Disease Pathogenesis

Imai, Yumiko; Kuba, Keiji; Ohto-Nakanishi, Takayo; Penninger, Josef

doi:10.1253/circj.cj-10-0045

Cited by 175 publications

(178 citation statements)

References 64 publications

(51 reference statements)

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“…This polymorphism was later classified as SNP rs4646994, and was shown to have a considerable influence on the level of ACE in plasma, where the D allele was associated with an elevated level (16, 18). For over two decades considerable interest had been directed to the study of I/D polymorphism in association with different disease states (19, 20). Several diseases were related to the frequency of I and D alleles and II, ID or DD genotypes of the ACE gene.…”

Section: Introductionmentioning

confidence: 99%

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

Al-Mukaynizi¹,

Alkhuriji²,

Babay³

et al. 2016

Journal of Medical Biochemistry

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SummaryBackgroundAn insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene has been associated with recurrent miscarriage (RM) in several populations. We initiated this study to determine the association, if any, between the I/D polymorphism of ACE gene and RM in Saudi females.MethodThis study was conducted on 61 Saudi females suffering from RM (mean age: 34.1±6.2 years; range 15–45) attending clinics at King Khalid University Hospital, and 59 age matched females who had at least 2 children, as controls. Blood samples were drawn in EDTA tubes by venipuncture. DNA was extracted using the Puregene DNA purification kits. Insertion/Deletion (I/D) polymorphism of ACE gene was investigated by amplifying the genomic DNA by PCR using gene-specific primers. A single 190 bp or 490 bp band was obtained in the homozygous cases for the D allele or I allele, respectively, while the presence of both 190 and 490 bp bands indicated heterozygosity (ID).Statistical analysisDeviation from Hardy-Weinberg equilibrium was determined (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). A standard chi-square (χ2) test was used for comparing the genotype and allele frequencies in the two groups and Students’t’ test and χ2 test were employed to compare values between the two groups. P<0.05 was considered statistically significant.ResultsThe frequencies of DD, ID, and II genotypes were 56.7%, 29.5% and 4.9%, respectively, in females with RM and 54.2%, 42.3% and 3.3% respectively in the control group, but the difference was not statistically significant.ConclusionIn some populations, meta-analyses showed an association between I/D polymorphism and RM risk, and the D allele was implicated as an increased risk factor for RM. However, this association was not apparent in the Saudi females.

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Section: Introductionmentioning

confidence: 99%

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

Al-Mukaynizi¹,

Alkhuriji²,

Babay³

et al. 2016

Journal of Medical Biochemistry

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“…In contrast to angiotensin converting enzyme (ACE), which synthesizes the potent vasoconstrictor, angiotensin II (Ang II) through its dicarboxypeptidase activity acting on the decapeptide angiotensin I, ACE2 catabolizes Ang II through its monocarboxypeptidase activity (Figure 1). Studies suggest ACE2 counters the adverse effects of ACE action and that these two enzymes play a ying and yang role in the physiological regulation of Ang II metabolism and in disease pathologies such as hypertension, progressive renal disease and diabetes [1,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17β-oestradiol-dependent and sex chromosome-independent

et al. 2010

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BackgroundAngotensin converting enzyme 2 (ACE2) is a newly discovered monocarboxypeptidase that counteracts the vasoconstrictor effects of angiotensin II (Ang II) by converting Ang II to Ang-(1-7) in the kidney and other tissues.MethodsACE2 activity from renal homogenates was investigated by using the fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH, where Mca is (7-methoxycoumarin-4-yl)-acetyl and Dnp is 2,4-dinitrophenyl.ResultsWe found that ACE2 activity expressed in relative fluorescence units (RFU) in the MF1 mouse is higher in the male (M) compared to the female (F) kidney [ACE2 (RFU/min/μg protein): M 18.1 ± 1.0 versus F 11.1 ± 0.39; P < 0.0001; n = 6]. Substrate concentration curves revealed that the higher ACE2 activity in the male was due to increased ACE2 enzyme velocity (Vmax) rather than increased substrate affinity (Km). We used the four core genotypes mouse model in which gonadal sex (ovaries versus testes) is separated from the sex chromosome complement enabling comparisons among XX and XY gonadal females and XX and XY gonadal males. Renal ACE2 activity was greater in the male than the female kidney, regardless of the sex chromosome complement [ACE2 (RFU/min/μg protein): intact-XX-F, 7.59 ± 0.37; intact-XY-F, 7.43 ± 0.53; intact-XX-M, 12.1 ± 0.62; intact-XY-M, 12.7 ± 1.5; n = 4-6/group; P < 0.0001, F versus M, by two-way ANOVA]. Enzyme activity was increased in gonadectomized (GDX) female mice regardless of the sex chromosome complement whereas no effect of gonadectomy was observed in the males [ACE2 (RFU/min/μg protein): GDX-XX-F, 12.4 ± 1.2; GDX-XY-F, 11.1 ± 0.76; GDX-XX-M, 13.2 ± 0.97; GDX-XY-M, 11.6 ± 0.81; n = 6/group]. 17β-oestradiol (E2) treatment of GDX mice resulted in ACE2 activity that was only 40% of the activity found in the GDX mice, regardless of their being male or female, and was independent of the sex chromosome complement [ACE2 (RFU/min/μg protein): GDX+E2-XX-F, 5.56 ± 1.0; GDX+E2-XY-F, 4.60 ± 0.52; GDX+E2-XX-M, 5.35 ± 0.70; GDX+E2-XY-M, 5.12 ± 0.47; n = 6/group].ConclusionsOur findings suggest sex differences in renal ACE2 activity in intact mice are due, at least in part, to the presence of E2 in the ovarian hormone milieu and not to the testicular milieu or to differences in sex chromosome dosage (2X versus 1X; 0Y versus 1Y). E2 regulation of renal ACE2 has particular implications for women across their life span since this hormone changes radically during puberty, pregnancy and menopause.

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“…Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a carboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7) [3,4]. ACE2 plays an important role in the vasoprotective axis (ACE2-Ang-(1-7)-Mas axis) of the renin angiotensin system (RAS) and counterbalances the vasoconstrictive, proliferative and fibrotic axes [ACE-Ang II-Ang II type 1 receptor (AT1R) axis] of the RAS [5,6,7].…”

Section: Introductionmentioning

confidence: 99%

The Changes of Serum Angiotensin-Converting Enzyme 2 in Patients with Pulmonary Arterial Hypertension due to Congenital Heart Disease

et al. 2013

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Background: Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in the renin-angiotensin system (RAS), has recently been found to have regulatory actions in hypoxic pulmonary hypertension and monocrotaline-induced pulmonary hypertension. We explored the hypothesis that the level of ACE2 protein contents may be decreased in patients with pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD). Objective: We observed the serum ACE2 protein contents in patients with PAH due to CHD (CHD-PAH), and investigated their correlation with mean pulmonary arterial pressure (mPAP). Methods: One hundred and four patients with CHD and 33 normal control patients (group A) were involved in the research. The patients with CHD were divided into 55 cases of nonpulmonary hypertension (group B), 25 cases of mild to moderate pulmonary hypertension (group C) and 24 cases of severe pulmonary hypertension (group D). The serum level of ACE2 protein contents were detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between these contents and mPAP were analyzed. Results: ACE2 protein contents significantly declined as mPAP increased. The mPAP was negatively correlated with the level of ACE2 protein contents. Conclusions: These results demonstrated that ACE2 may play an important regulatory role in CHD-PAH.

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Angiotensin-Converting Enzyme 2 (ACE2) in Disease Pathogenesis

Cited by 175 publications

References 64 publications

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17β-oestradiol-dependent and sex chromosome-independent

The Changes of Serum Angiotensin-Converting Enzyme 2 in Patients with Pulmonary Arterial Hypertension due to Congenital Heart Disease

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