Angiotensin converting enzyme (ACE) plays an important role in the physiology of vasculature, blood pressure and inflammation. ACE gene, known to have insertion/deletion (I/D) polymorphism, has been widely investigated in its relation with cardiovascular and neurodegenerative diseases and longevity. ACE gene polymorphism in an inflammation associated osteoarthritis (OA) patients is not known. Here we have investigated ACE gene polymorphism in 142 Korean primary knee OA patients and 135 healthy volunteers to establish any clinical correlates between ACE polymorphism and knee osteoarthritis. Clinical parameters such as disease onset age, Kellgren-Lawrence grade and Lequesne's functional index provided additional analysis of the relationship of ACE polymorphism and clinical features of OA. Early onset OA showed significantly higher allele frequency and carriage rate of I than late onset OA. Radiographically severe and functionally poor OA showed higher carriage rate of I allele than radiographically mild and functionally good OA, respectively. This study first reports ACE gene polymorphism to be a risk factor for early onset, severe form primary knee OA.
Adult ; Aged ; Female ; Human ; Male ; Middle Aged ; Osteoarthritis, Knee/*genetics ; Peptidyl-Dipeptidase A/blood/*genetics ; *Polymorphism (Genetics)

Child ; Child, Preschool ; Female ; Humans ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Sleep Apnea, Obstructive ; genetics ; physiopathology

Adult ; Genotype ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; blood ; genetics ; Pneumoconiosis ; blood ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVEAngiotensin converting enzyme 2 (ACE2) efficiently hydrolyses the potent vasoconstrictor angiotensin II to vasodilative angiotensin (1-7). We hypothesized that ACE2 overexpression may inhibit inflammation response in atherosclerotic plaque by degrading Ang II into Ang-(1-7).

METHODSAtherosclerosis (AS) plaques were induced in the abdominal aorta of 38 rabbits by endothelial injury and atherogenic diet for 3 months. Rabbits were then underwent injection of a recombinant adenovirus (2.5 x 10(9) pfu/ml) carrying a murine ACE2 gene (Ad-ACE2) through a catheter into the abdominal aortic segments rich in plaques (n = 19) or injection of a control vector Ad-EGFP (n = 19). One month later, all rabbits were sacrificed and plaques from aortic segments were analyzed.

RESULTSACE2 expression in aortic tissues of the Ad-ACE2 group were confirmed by immunohistochemistry. Macrophage infiltration (13.6% +/- 4.2% vs. 23.6% +/- 6.9%, P < 0.01) and MCP-1 expression (13.2% +/- 0.4% vs. 25.0% +/- 7.4%, P < 0.01) were significantly reduced in Ad-ACE2 group compared to Ad-EGFP group.

CONCLUSIONSOverexpression of ACE2 inhibited atherosclerotic plaque inflammation response in hypercholesterolemic rabbits.

Animals ; Atherosclerosis ; genetics ; metabolism ; Cells, Cultured ; Diet, Atherogenic ; Genetic Vectors ; Peptidyl-Dipeptidase A ; genetics ; Rabbits ; Transfection

OBJECTIVETo study the relationship between insertion/deletion (I/D) polymorphism of 287 bp in the 16th intron of angiotensin converting enzyme (ACE) and essential hypertension in children.

METHODSI/D polymorphism of 287 bp in the 16th intron of ACE was detected using PCR in 105 children with essential hypertension and 105 normal children as control group.

RESULTSThere was an I/D polymorphism in the 16th intron of ACE in the hypertension and the control groups: type II, type ID and type DD. The genotype frequencies of type DD, type ID and type II in the hypertension group were 30.5%, 47.6% and 21.9%, respectively. The genotype frequencies of type DD, type ID and type II in the control group were 14.3%, 46.7% and 39.1%, respectively. There were significant differences in the genotype frequencies of types DD and II between the two groups (P<0.01). The allele frequency of type D (54.3% vs 37.6%) was significantly higher in the hypertension group; in contrast, the allele frequency of type I (45.7% vs 62.4%) was significantly lower than in the control group (P<0.01).

CONCLUSIONSPolymorphism of type II, type ID and type DD exits in ACE. The deletion of 287 bp in the 16th intron of ACE might be associated with the occurrence of essential hypertension in children.

Adolescent ; Child ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic

Adult ; Asian Continental Ancestry Group ; genetics ; Female ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic

Coronaviruses are single-stranded RNA viruses that are common in animals. In the past 20 years, there have been three large-scale epidemics of coronaviruses, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease (COVID). Heart disease is an independent risk factor for severe COVID. At the same time, SARS-CoV-2 infection is often complicated with myocardial injury, which is closely related to poor prognosis. The receptors of SARS coronavirus are angiotensin-converting enzyme 2 (ACE2) and CD209L, among which ACE2 is the main receptor, and ACE2 is abundant in the heart. The receptor of MERS-coronavirus is dipeptide peptidase 4 (DPP4), which is not expressed in myocardial cells, but existed in vascular endothelial cells and blood. These receptors are important factors for the myocardial injury caused by coronavirus infection.
Animals ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; SARS-CoV-2 ; Endothelial Cells ; Peptidyl-Dipeptidase A/genetics*

We tested the hypothesis that angiotensin-converting enzyme (ACE) and angiotensinogen gene polymorphism influence the incidence, development and outcome of preeclampsia. Subjects were recruited from 90 Korean patients with preeclampsia during pregnancy and 98 age-matched controls. After isolation of DNA, polymerase chain reactions (PCR) were carried out to detect polymorphism of the ACE and angiotensinogen. M235T and T174M genotypes of angiotensinogen were determined by digestion with restriction enzyme endonuclease Tth 111-I and NCo I, respectively. The frequency of DD genotype was significantly greater in preeclampsia (0.36) than in controls (0.14) (p<0.05). The frequency of D allele was 0.55 in preeclampsia and 0.40 in controls (p<0.05). There were no differences in the onset of preeclampsia and pregnancy outcomes according to the ACE genotypes. There was no difference in the frequency of a allele of angiotensinogen M235T between the groups (0.79:0.78 in preeclampsia : controls). The frequency of T allele of angiotensinogen T174M gene was slightly increased, but not significantly, in preeclampsia (0.11) than in controls (0.07). In a multivariate analysis, only ACE genotype was associated with the development of preeclampsia (beta=0.27, p=0.05). In conclusion, a molecular variant of ACE, but not angiotensinogen, gene is associated with preeclampsia in Korean women.
Adult ; Angiotensinogen/*genetics ; Female ; Gene Frequency ; Genotype ; Human ; Korea ; Peptidyl-Dipeptidase A/*genetics ; *Polymorphism (Genetics) ; Pre-Eclampsia/*genetics ; Pregnancy

Angiotensin I-converting enzyme (ACE, EC3.4.15.1) plays an important role in regulating blood pressure. The C-domain of ACE has been identified as the main catalytic site of angiotensin I cleavage in vivo. The ACE gene fragment of the C-domain was amplified by PCR and cloned into the pPIC9K secretory expression plasmid. The recombinant plasmid was transformed into Pichia pastoris strain GS115. Positive clones were selected and subject to electroporation. Antibiotic G418 was used for the screening of multicopy inserts. After optimization of the expression system, the protein yield reached 0.5 g/L by flask-shaking culture fermentation, and enzyme activity reached 7.178 U/mL in the fermentation supernatant. The purity of the target protein obtained was 97% after Ni+ affinity chromatography. Enzyme inhibitory activity assay using Captopril showed that it is promising to use ACE-C domain as new generation of target for screening ACE inhibitor antihypertensive drugs.
Angiotensin-Converting Enzyme Inhibitors ; Catalytic Domain ; genetics ; Electroporation ; Humans ; Peptidyl-Dipeptidase A ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics

To investigate the distribution frequencies of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II I type receptor (AT1R) genotypes in Chinese, to find the relationships between polymorphisms of ACE, AGT and AT1R gene, and coronary artery thrombosis disease (CATD) and to study the interactions of themselves, PCR and PCR-RFLP techniques were performed to determine the genotypes of ACE, AGT and AT1R gene in CATD group (192 cases) and control group (110 cases). The results showed that (1) genotype frequencies of the three polymorphisms in the control group were 12.2% (DD), 43.9% (ID), and 43.9% (II) for the ACE I/D polymorphism; 8.2% (MM), 36.7% (MT), and 55.1% (TT) for AGT M235T polymorphism; 91.8% (AA), 8.2% (AC) for AT1R A1166C polymorphism respectively; (2) there were no significant differences between patients in either the control group, the non-MI group, or the MI group in any genotype frequency of all these three genes (P >0.05). (3) the odds ratio for CATD in subjects carrying both AT1R-AC and AGT-TT genotype was 3.517 (95% CI 0.988 - 12.527), compared with those carrying AT1R-AA and AGT-TT genotype and was 15.000 (95% CI 1.940-115.963), compared with those carrying AT1R-AC and AGT-MM/MT genotype. In subjects with AT1R-AC genotype, there was also a great difference of ACE D allele frequency between control group and CATD group (P=0.017). It is concluded that genotype frequencies of ACE I/D polymorphism, AGT M235T polymorphism, and AT1R A1166C polymorphism were obviously different from those in western countries. Although these three polymorphisms were not independent risk factors for CATD or myocardial infarction (MI) in Chinese, AT1R-AC genotype has a significant synergistic effect with AGT-TT genotype. There is also a obvious interaction between AT1R-AC genotype and ACE D allele.
Angiotensinogen ; genetics ; Coronary Thrombosis ; genetics ; Genotype ; Humans ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1 ; genetics