Effect of angiotensin converting enzyme gene polymorphism on patients with in-stent restenosis after percutaneous coronary intervention

Purpose: To evaluate the association between common single nucleotide polymorphisms (SNPs) in angiotensin converting enzyme (ACE) gene and the risk of in-stent restenosis (ISR) and/or the response to angiotensin converting enzyme inhibitor ACEI in individuals with stable coronary artery disease (CAD) after stent implantation. Methods: The total population of this study consisted of 200 Egyptian individuals divided into 2 groups - in-stent restenosis (ISR) and non ISR group). Genomic DNA was withdrawn from EDTA whole blood applying a spin column approach and ACE gene insertion/deletion (I/D) polymorphisms were determined by polymerase chain reaction (PCR). Results: Carriers of allele D of ACE gene were significantly more liable to ISR occurrence. However, carriers of allele I were significantly more liable to ISR occurrence after administration of ACEI. There is a negative interaction between DD genotype of ACE gene and ACEI administration on ISR after percutaneous coronary intervention (PCI). However, there is a positive interaction between II and ID genotype of ACE gene and ACEI administration on ISR after PCI with bare metal stents (BMS). Conclusion: It is beneficial to implement ACEI in therapeutic regimen in individuals with ID or II genotypes of ACE gene, especially with BMS implementation.

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

Angiotensin-Converting Enzyme Genotype–Specific Immune Response Contributes to the Susceptibility of COVID-19: A Nested Case–Control Study

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has resulted in a global pandemic.Methodology: We used a two-step polymerase chain reaction to detect the ACE genotype and ELISA kits to detect the cytokine factor. We also used proteomics to identify the immune pathway related to the ACE protein expression.Result: In this study, we found that the angiotensin-converting enzyme (ACE) deletion polymorphism was associated with the susceptibility to COVID-19 in a risk-dependent manner among the Chinese population. D/D genotype distributions were higher in the COVID-19 disease group than in the control group (D/D odds ratio is 3.87 for mild (p value < 0.0001), 2.59 for moderate (p value = 0.0002), and 4.05 for severe symptoms (p value < 0.0001), logic regression analysis. Moreover, genotype-specific cytokine storms and immune responses were found enriched in patients with the ACE deletion polymorphism, suggesting the contribution to the susceptibility to COVID-19. Finally, we identified the immune pathway such as the complement system related to the ACE protein expression of patients by lung and plasma proteomics.Conclusion: Our results demonstrated that it is very important to consider gene polymorphisms in the population to discover a host-based COVID-19 vaccine and drug design for preventive and precision medicine.

Stimulation of Angiotensin Converting Enzyme 2: A Novel Treatment Strategy for Diabetic Nephropathy

Despite current therapies for diabetic nephropathy, many patients continue to progress to end-stage renal disease requiring renal replacement therapy. While the precise mechanisms underlying diabetic nephropathy remain to be determined, it is well established that chronic activation of the renin angiotensin aldosterone system (RAAS) plays a substantial role in the pathogenesis of diabetic nephropathy. Angiotensin converting enzyme 2 (ACE2), the enzyme responsible for activating the reno-protective arm of the RAAS converts angiotensin (Ang) II into Ang 1-7 which exerts reno-protective effects. Chronic RAAS activation leads to kidney inflammation and fibrosis, and ultimately lead to end-stage kidney disease. Currently, angiotensin converting enzyme inhibitors and Ang II receptor blockers are approved for renal fibrosis and inflammation. Targeting the reno-protective arm of the RAAS should therefore, provide further treatment options for kidney fibrosis and inflammation. In this review, we examine how targeting the reno-protective arm of the RAAS can ameliorate kidney inflammation and fibrosis and rescue kidney function in diabetic nephropathy. We argue tissue ACE2 stimulation provides a unique and promising therapeutic approach for diabetic nephropathy.

Co-Expression and Localization of Angiotensin-Converting Enzyme-2 (ACE2) and the Transmembrane Serine Protease 2 (TMPRSS2) in Paranasal Ciliated Epithelium of Patients with Chronic Rhinosinusitis

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme-2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) as a primary receptor for invasion. Cell entry by the virus requires the co-expression of these molecules in the host cells. Objective We investigated ACE2 and TMPRSS2 expression and localization in paranasal epithelium of eosinophilic chronic rhinosinusitis (ECRS) patients (n = 38), non-ECRS (n = 31), and healthy controls (n = 25). CRS inflammatory patterns are characterized by the type of cytokines; we investigated whether inflammatory endotypes are associated with cell-entry molecules, as this could be linked to susceptibility to SARS-CoV-2 infection. Methods The ACE2, TMPRSS2, and other inflammatory cytokine mRNA levels were assessed by quantitative RT-PCR. The localizations of ACE2- and TMPRSS2-positive cells were examined with immunofluorescent double-staining using laser scanning confocal microscopy (LSCM). Results The non-ECRS patients showed significantly increased ACE2 and TMPRSS2 mRNA expressions compared to the ECRS patients. The CRS patients’ ACE2 and TMPRSS2 mRNA levels were positively correlated with IFN-γ ( r = 0.3227 and r = 0.3264, respectively) and TNF-α ( r = 0.4008, r = 0.3962, respectively). ACE2 and TMPRSS2 were negatively correlated with tissue eosinophils ( r = −0.3308, r = −0.3112, respectively), but not with IL-13. ACE2 mRNA levels were positively correlated with TMPRSS2 ( r = 0.7478). ACE2 and TMPRSS2 immunoreactivities were localized mainly in the epithelial ciliated cells, as confirmed by co-staining with TMPRSS2 and acetylated α-tubulin, a cilia organelle marker. Using LSCM imaging, we observed higher expressions of these molecules in the non-ECRS patients versus the ECRS patients. Conclusion ECRS patients with type 2 inflammation showed decreased ACE2 and TMPRSS2 expressions in their sinus mucosa. ACE2 and TMPRSS2 regulation seems to be positively related to IFN-γ and TNF-α production in CRS patients; ACE2 and TMPRSS2 were co-expressed in the ciliated epithelium of their paranasal mucosa, implicating the paranasal epithelium as a portal for initial infection and transmission.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research database, a primary care database in the UK. In this study, 53,832 and 43,106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio (SMR) weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) of developing AMD. During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 and 2.2 per 1,000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (aHR: 1.07 (95% CI 0.90-1.27) and 0.87 (0.71-1.07) respectively).