Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome

Hoshida, Shiro; Kato, Junji; Nishino, Masami; Egami, Yasuyuki; Takeda, Toshihiro; Kawabata, Masayoshi; Tanouchi, Jun; Yamada, Yoshio; Kamada, Takenobu

doi:10.1161/01.cir.103.5.630

Cited by 73 publications

(36 citation statements)

References 13 publications

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“…Although there is a general consensus that inhibition of endothelial ACE is important for the benefits of any ACEi, inhibition of adventitial ACE may be just as important especially in clinical management of hypertension, heart failure, and/or ischemic heart disease or coronary atherosclerosis, because these disorders are associated with vascular hypertrophy, left ventricular remodeling, and atherosclerotic plaque formation. A recent report indicated that coronary artery ACE activity was approximately 5-fold higher in patients with acute coronary syndrome even though serum ACE activity was not different, 6 suggesting that inhibition of vascular and/or cardiac ACE is very important for the clinical benefits of ACEi.…”

Section: Discussionmentioning

confidence: 99%

“…A deletion polymorphism in the ACE gene (DD) has been linked to increased circulating and tissue levels of ACE, 5 and indeed ACE activity is markedly increased in coronary arteries of patients with acute coronary syndrome. 6 High levels of circulating and tissue ACE may lead to increased tissue Ang II formation in the vascular wall, which induces vascular injury and subsequent hypertrophy and stenosis. Beneficial effects of ACEi may also be associated with increased bioavailability of nitric oxide (NO) in high-risk patients with ischemic heart disease.…”

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confidence: 99%

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Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

2002

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Abstract-Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT 1 receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (nϭ7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT 1 receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT 1 receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT 1 receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension (Hypertension. 2002;39[part 2]:634-638.)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

2002

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“…Interestingly, ACE activity was significantly increased in the culprit coronary lesions of patients with acute coronary syndrome compared with patients with stable ischemic heart disease. 96 Intervention studies in atherosclerotic animal models have shown the atherogenic effect of Ang II and the antiatherogenic effect of ACE inhibitors. Continuous administration of Ang II to ApoE Ϫ/Ϫ mice significantly increased lesion size.…”

Section: Ace and Atherosclerosismentioning

confidence: 99%

Angiotensin-Converting Enzyme and Vascular Remodeling

Heeneman

Sluimer

Daemen

2007

Circulation Research

189

132

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Abstract-Vascular remodeling is the result of a close interplay of changes in vascular tone and structure. In this review, the role of angiotension-converting enzyme (ACE) and the impact of ACE inhibition on vascular remodeling processes during vascular injury and restenosis, hypertension, atherosclerosis, and aneurysm formation are discussed. The role of ACE and angiotensin II (Ang II) in neointimal thickening has been firmly established by animal studies and is mediated by Ang II type 1 (AT 1 ) receptor signaling events via monocyte chemoattractant protein-1 and NAD(P)H oxidase. ACE and Ang II are involved in the remodeling of large and resistance arteries during hypertension; here, cell proliferation and matrix remodeling are also regulated by signaling events downstream of the AT 1 receptor. In atherosclerosis, Ang II is involved in the inflammatory and tissue response, mediated by various signaling pathways downstream of the AT 1 receptor. Although ACE inhibition has been shown to inhibit atherosclerotic processes in experimental animal models, results of large clinical trials with ACE inhibitors were not conclusive. Remodeling of vessel dimensions and structure during aneurysm formation is counteracted by ACE inhibition. Here, a direct effect of ACE inhibitors on matrix metalloproteinase activity has to be considered as part of the working mechanism. The role of ACE2 in vascular remodeling has yet to be established; however, ACE2 has been shown to be associated with vascular changes in hypertension and atherosclerosis. (Circ Res. 2007;101:441-454.)

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“…This is akin to the phenomenon of upregulation of receptors when they are exposed constantly to an antagonist drug. The second possibility is that progressive atherosclerosis in the vasculature induces ACE activity [14][15][16]. However, overt atherosclerosis is not prominent in brachial arteries, although there may be enough progressive vascular/endothelial dysfunction to induce local ACE activity.…”

Section: Discussionmentioning

confidence: 99%

Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus

2007

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Aims/hypothesis In chronic heart failure there is gradual reactivation of vascular tissue angiotensin I (AI) to angiotensin II (AII) conversion over time in patients taking chronic ACE inhibitor therapy. However, it remains unknown whether the same overall phenomenon occurs in other patients taking chronic ACE inhibitor therapy, such as patients with type 2 diabetes mellitus. Methods We studied 30 patients with type 2 diabetes mellitus (mean age 43.5±10.8 years), all of whom received lisinopril (20 mg/day) as part of their normal treatment. Over the course of the 18 month study, we made measurements at 0, 9 and 18 months. These measurements included plasma values for components of the renin-angiotensinaldosterone system. In addition, we infused AI and AII into the brachial arteries of patients to assess vascular tissue AI to AII conversion. Results There were no significant changes in plasma renin activity, ACE, AI, AII or aldosterone during the study. In contrast, vascular AI to AII conversion was significantly (p= 0.01) greater at 18 months than at 0 months. There was no change over time in the response to infused AII. Conclusions/interpretation We have shown in vivo that vascular tissue AI to AII conversion gradually increases over time in patients with type 2 diabetes being treated with lisinopril. Further studies are required to determine whether this reactivation detracts from the cardioprotective effects of chronic ACE inhibitor therapy in diabetic patients, and if so, how best to overcome it.

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Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome

Abstract: The present study demonstrates increased ACE activity in culprit lesions in acute coronary syndrome, indicating that enhanced ACE activity is related to the causative mechanism of active coronary lesions.

Cited by 73 publications

References 13 publications

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Angiotensin-Converting Enzyme and Vascular Remodeling

Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus

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Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome

Abstract: The present study demonstrates increased ACE activity in culprit lesions in acute coronary syndrome, indicating that enhanced ACE activity is related to the causative mechanism of active coronary lesions.

Cited by 73 publications

References 13 publications

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT 1 Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT 1 Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Angiotensin-Converting Enzyme and Vascular Remodeling

Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus

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Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease