scholarly journals Improved renal cancer prognosis among users of drugs targeting renin-angiotensin system

2021 ◽  
Author(s):  
Tommi Eskelinen ◽  
Thea Veitonmäki ◽  
Andres Kotsar ◽  
Teuvo L. J. Tammela ◽  
Antti Pöyhönen ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Metastatic Tumor ◽  
Drug Group ◽  
High Dose ◽  
Defined Daily Dose ◽  
Prescription Database ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Tumor Extent

Abstract Purpose We explored renal cell cancer (RCC) survival among users of antihypertensive medication as hypertension is proposed to be a risk factor for RCC and ACE-inhibitors and angiotensin receptor blockers (ARBs) have been associated with improved prognosis of RCC. Methods Finnish cohort of 13,873 participants with RCC diagnosed between 1995–2012 was formed from three national databases. RCC cases were identified from Finnish Cancer Registry, medication usage from national prescription database and co-morbidities from Care Registry of Healthcare. Logistic regression was used to calculate odds ratios for metastatic tumor extent at the time of diagnosis. Risk of RCC specific death after diagnosis was analyzed using Cox regression adjusted for tumor clinical characteristics. Results A total of 5,179 participants died of RCC during the follow-up. No risk association was found for metastatic tumor extent for any drug group. ACE-inhibitors, but no other drug group were associated with decreased risk of RCC specific death overall (HR 0.88, 95% CI 0.82–0.95) compared to non-users. In time-dependent analysis high-dose use of ACE-inhibitors (392 Defined Daily Dose (DDD)/year), HR 0.54, 95% CI 0.45–0.66) and ARBs (786.1 DDD/year, HR 0.66, 95% CI 0.50–0.87) associated with improved RCC survival. No information of TNM-classification or tobacco smoking was available. Conclusion ACE-inhibitors and ARBs in high dose associated with improved RCC specific survival. This may reflect overall benefit of treating hypertension with medication targeting renin-angiotensin system (RAS) system among RCC patients. Further studies are needed to explore the role of RAS in RCC.

Imbalance of the renin–angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

Gut ◽  
2019 ◽  
Vol 69 (5) ◽  
pp. 841-851 ◽  
Author(s):  
Mayur Garg ◽  
Simon G Royce ◽  
Chris Tikellis ◽  
Claire Shallue ◽  
Duygu Batu ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Intestinal Inflammation ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease Outcomes ◽  
Collagen Secretion

ObjectiveWe evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.DesignCultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1–7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies.ResultsHuman colonic myofibroblast proliferation was reduced by Ang (1–7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1–7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson’s trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=−0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation.ConclusionsThe RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

scholarly journals Hematological Side Effects of ACE Inhibitors and a Hypothetical Local Renin-Angiotensin System in the Bone Marrow

Nephron ◽  
1997 ◽  
Vol 77 (1) ◽  
pp. 111-111 ◽  
Author(s):  
&Idot;brahim C. Haznedaro&gbreve;lu ◽  
&Idot;brahim H. G&uuml;ll&uuml;
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

2021 ◽  
Vol 22 (24) ◽  
pp. 13178
Author(s):  
Duc Le ◽  
Lindsay Brown ◽  
Kundan Malik ◽  
Shin Murakami
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Heart Association ◽  
Model Systems ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Amyloid Toxicity ◽  
Age Related

A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events.

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