Firibastat: A Novel Brain Aminopeptidase Inhibitor – A New Era of Antihypertensive therapy

Gupta, Rahul; Alcantara, Ryan; Popli, Tarun; Tariq, Umair; Sood, Aayaan; Mahajan, Sanjeev; Ayele, Hiwot; Rajeswaran, Yasotha; Vyas, Apurva

doi:10.1016/j.cpcardiol.2021.100859

Cited by 12 publications

(8 citation statements)

References 52 publications

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“…The above-described mechanistic proposals have presented a pathogenetic substrate, showing how H. pylori infection may possibly exert its action and influence MetS-related arterial hypertension. Further research is warranted, however, to elucidate in depth the potential impact of Helicobacter pylori-related MetS on arterial hypertension, a serious public health problem with high global incidence and prevalence that continues to increase and may contribute to globally high levels of morbidity and mortality [1].…”

Section: Discussionmentioning

confidence: 99%

“…Arterial hypertension is one of the most important components of the metabolic syndrome (MetS) and represents a global major health burden with implications for individual and public health, as well as direct and indirect healthcare costs. It is a substantial factor for the development of atherosclerosis, with a high global incidence and prevalence that continues to increase and contributes to worldwide morbidity and mortality [1]. It constitutes a major risk factor for MetS-related cardiovascular disease and the leading cause of mortality related with MetS-associated chronic kidney failure, ischemic heart disease and stroke [2,3].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

et al. 2021

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Arterial hypertension is a risk factor for several pathologies, mainly including cardio-cerebrovascular diseases, which rank as leading causes of morbidity and mortality worldwide. Arterial hypertension also constitutes a fundamental component of the metabolic syndrome. Helicobacter pylori infection is one of the most common types of chronic infection globally and displays a plethora of both gastric and extragastric effects. Among other entities, Helicobacter pylori has been implicated in the pathogenesis of the metabolic syndrome. Within this review, we illustrate the current state-of-the-art evidence, which may link several components of the Helicobacter pylori-related metabolic syndrome, including non-alcoholic fatty liver disease and arterial hypertension. In particular, current knowledge of how Helicobacter pylori exerts its virulence through dietary, inflammatory and metabolic pathways will be discussed. Although there is still no causative link between these entities, the emerging evidence from both basic and clinical research supports the proposal that several components of the Helicobacter pylori infection-related metabolic syndrome present an important risk factor in the development of arterial hypertension. The triad of Helicobacter pylori infection, the metabolic syndrome, and hypertension represents a crucial worldwide health problem on a pandemic scale with high morbidity and mortality, like COVID-19, thereby requiring awareness and appropriate management on a global scale.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

et al. 2021

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“…However, further research is warranted to elucidate in depth the mechanisms involved in Hp -related arterial hypertension, a serious clinical disorder with high worldwide incidence and prevalence that continues to increase and contributes to global morbidity and mortality [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-Related Metabolic Parameters and Premalignant Gastric Mucosa Histological Lesions in Swiss Bariatric Patients

et al. 2021

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Obesity, as a major risk factor of metabolic syndrome (MetS), represents a pandemic, especially in Western societies, and is considered a risk factor for malignancies. Helicobacter pylori (Hp), is a definite carcinogen with global distribution. We aimed to investigate, for the first time in Switzerland, the main gastric mucosa premalignant histological lesions of bariatric patients in correlation with MetS components and Hp Infection (Hp-I). By reviewing retrospectively 94304 patient cases, a total of 116 eligible patients having undergone bariatric surgery were identified. The mean patient age was 48.66 years. Hp(+) patients were 24% (28/116). Presence of gastric mucosa atrophy was documented in 8/28 Hp(+) patients (29%) and (2/88) Hp(−) ones (2%) (p = 0.006). Gastric mucosa intestinal metaplasia was observed in 14/28 (50%) Hp(+) patients versus 3/88 (3.4%) of Hp(-) group (p < 0.0001). Hp(+) patients exhibited statistically higher arterial hypertension (p = 0.033). The homeostatic model of assessment insulin resistance was also statistically significantly higher for the Hp(+) group (p < 0.001). In a multivariate analysis, including arterial hypertension, gastric mucosa atrophy, and intestinal metaplasia as variables, statistical significance remained only for intestinal metaplasia (p = 0.001). In conclusion, Hp-I is associated with premalignant gastric mucosa histologic lesions and MetS components, including arterial hypertension and IR. Further large-scale prospective studies are required to confirm these findings.

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“…This is due to the fact that centrallyacting APA inhibitors are antihypertensive and not hypotensive agents, decreasing BP only in hypertensive but not in normotensive animals, nor in human volunteers. 14,36,37 On the other hand, we recently described an additional mechanism of action of firibastat in the control of BP, involving ACE2 and angiotensin 1-7 (Ang1-7) 38 . Our findings suggest that in the brain, the increase in ACE2 activity resulting from APA inhibition by firibastat treatment, subsequently increasing conversion of brain AngII into Ang1-7 and activating the Mas receptor while blocking brain AngIII formation, contributes to the antihypertensive effect and the decrease in AVP release induced by firibastat.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

QGC606: A Best-in-Class Orally Active Centrally Acting Aminopeptidase A Inhibitor Prodrug for Treating Heart Failure Following Myocardial Infarction

Boitard

Keck²,

Deloux³

et al. 2022

Canadian Journal of Cardiology

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Firibastat: A Novel Brain Aminopeptidase Inhibitor – A New Era of Antihypertensive therapy

Cited by 12 publications

References 52 publications

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

Helicobacter pylori-Related Metabolic Parameters and Premalignant Gastric Mucosa Histological Lesions in Swiss Bariatric Patients

QGC606: A Best-in-Class Orally Active Centrally Acting Aminopeptidase A Inhibitor Prodrug for Treating Heart Failure Following Myocardial Infarction

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