Serum levels of renin-angiotensin system components in acute stroke patients

Mogi, Masaki; Kawajiri, Masakazu; Tsukuda, Kana; Matsumoto, Shoji; Yamada, Takeshi; Horiuchi, Masatsugu

doi:10.1111/ggi.12167

Cited by 23 publications

(14 citation statements)

References 23 publications

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“…One recent study found that serum ACE2 levels within the first 24 hours post-stroke differ slightly by stroke subtype with lacunar exhibiting lower levels than cardioembolic strokes. 5 In rats, expression and activity of ACE2 in ischemic brain tissue is altered, 6 and we demonstrated that serum ACE2 activity is initially decreased, followed by rebound increases over the next several days. 4 Validating this decrease in human disease will provide further support for targeting ACE2 with neuroprotective interventions.…”

Section: Introductionmentioning

confidence: 71%

Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke

Bennion

Rosado

Haltigan

et al. 2016

J Renin Angiotensin Aldosterone Syst

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Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, are dynamically altered after stroke in preclinical models. We sought to characterize the previously unexplored changes in serum ACE2 activity of stroke patients and the mechanism of these changes. Serum samples were obtained from patients during acute ischemic stroke (n=39), conditions mimicking stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity levels were analyzed by fluorometric assay and correlated with clinical variables by regression analyses. Serum ACE2 activity was significantly lower in acute ischemic stroke as compared to both control and stroke-alert patients, followed by an increase to control levels at three days. Serum ACE2 activity significantly correlated with the presence of ischemic stroke after controlling for other factors (P=0.01). Additional associations with ACE2 activity included a positive correlation with systolic blood pressure at presentation in stroke-alert (R2=0.24, P=0.03), while stroke levels showed no correlation (R2=0.01, P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic changes in serum ACE2 activity in stroke, which concur with preclinical studies, are not likely to be driven primarily by acute changes in blood pressure or sheddase activity. These findings provide new insight for developing therapies targeting this protective system in ischemic stroke.

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Section: Introductionmentioning

confidence: 71%

Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke

Bennion

Rosado

Haltigan

et al. 2016

J Renin Angiotensin Aldosterone Syst

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“…Higher levels of ACE2 were found among patients who experienced cardioembolic stroke versus other stroke subtypes 18 , although baseline or control ACE2 levels were not assessed for comparison. It has also been shown that ACE2 gene polymorphisms may be associated with increased risk for stroke 19 .…”

Section: Discussionmentioning

confidence: 99%

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

et al. 2015

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The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis represents a promising target for inducing stroke neuroprotection. Here, explored stroke-induced changes in expression and activity of endogenous angiotensin converting enzyme 2 and other system components in Sprague Dawley rats. To evaluate the clinical feasibility of treatments that target this axis and that may act in synergy with stroke-induced changes, we also tested the neuroprotective effects of diminazene aceturate, an angiotensin converting enzyme 2 activator, administered systemically post-stroke. Amongst rats that underwent experimental endothelin-1-induced ischemic stroke, angiotensin converting enzyme 2 activity in the cerebral cortex and striatum increased in the 24 hours after stroke. Serum angiotensin converting enzyme 2 activity was decreased within 4h post stroke, but rebounded to reach higher than baseline levels 3d post-stroke. Treatment following stroke with systemically-applied diminazene resulted in decreased infarct volume and improved neurological function without apparent increases in cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist, resulted in larger infarct volumes in diminazene-treated rats, and central infusion of the angiotensin converting enzyme 2 inhibitor MLN-4760 alone worsened neurological function. The dynamic alterations of the protective angiotensin converting enzyme 2 pathway following stroke suggest that it may be a favorable therapeutic target. Indeed, significant neuroprotection resulted from post-stroke angiotensin converting enzyme 2 activation, likely via Mas signaling in a blood flow-independent manner. Our findings suggest that stroke therapeutics that target the angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis may interact cooperatively with endogenous stroke-induced changes, lending promise to their further study as neuroprotective agents.

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“…Nevertheless, it remains unknown whether circulating ACE2 levels have any relationship with ACE2 abundance in the respiratory system or intestinal tissues. Moreover, circulating ACE2 levels are increased in patients with cardiovascular diseases (CVDs), including heart failure [ 66 , 67 ] and arterial fibrillation [ 68 ], chronic kidney disease (CKD) [ 69 ], atherosclerosis [ 70 ], and stroke [ 71 ]. In addition, circulating ACE2 levels are reported to be higher in male than in female patients with heart failure [ 72 ].…”

Section: Covid-19 and Ace2mentioning

confidence: 99%

Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19

et al. 2020

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Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than seven million people worldwide, contributing to 0.4 million deaths as of June 2020. The fact that the virus uses angiotensin-converting enzyme (ACE)-2 as the cell entry receptor and that hypertension as well as cardiovascular disorders frequently coexist with COVID-19 have generated considerable discussion on the management of patients with hypertension. In addition, the COVID-19 pandemic necessitates the development of and adaptation to a “New Normal” lifestyle, which will have a profound impact not only on communicable diseases but also on noncommunicable diseases, including hypertension. Summarizing what is known and what requires further investigation in this field may help to address the challenges we face. In the present review, we critically evaluate the existing evidence for the epidemiological association between COVID-19 and hypertension. We also summarize the current knowledge regarding the pathophysiology of SARS-CoV-2 infection with an emphasis on ACE2, the cardiovascular system, and the kidney. Finally, we review evidence on the use of antihypertensive medication, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19.

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Serum levels of renin-angiotensin system components in acute stroke patients

Abstract: These findings suggest that changes of serum RAS components could reflect stroke subtypes and predict stroke severity.

Cited by 23 publications

References 23 publications

Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke

Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19

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