Interference of Angiotensin-Converting Enzyme Inhibitors on Erythropoiesis in Kidney Transplant Recipients

Morrone, L F; Paolo, Salvatore Di; Logoluso, Francesco; Schena, Antonio; Stallone, Giovanni; Giorgino, Francesco; Schena, Francesco Paolo

doi:10.1097/00007890-199709270-00021

Cited by 77 publications

(67 citation statements)

References 37 publications

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“…In a rat model of cardiac hypertrophy by aortocaval shunt, IGF-I binding to its receptor in the myofibers was elevated, and treatment with an ACE inhibitor (captopril) or an ARB (losartan) resulted in regression of cardiac hypertrophy accompanied by an attenuation or normalization of increased IGF-I affinity (162). In kidney transplant patients with posttransplant erythrocytosis, treatment with ACE inhibitors reduced both the hematocrit and serum IGF-I; hematocrit and circulating IGF-I levels were positively related, suggesting that IGF-I contributes to the ACE inhibitor-induced decrease of hematocrit in these patients (295).…”

Section: Ras and Igf Signalingmentioning

confidence: 99%

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Cavanagh

Inserra

Ferder

2015

American Journal of Physiology-Heart and Circulatory Physiology

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de Cavanagh EM, Inserra F, Ferder L. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am J Physiol Heart Circ Physiol 309: H15-H44, 2015. First published May 1, 2015; doi:10.1152/ajpheart.00459.2014, renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca 2ϩ , phosphate, and vitamin D metabolism, and their dysregulation may participate in age-related disease. Here we review how mTOR inhibition extends lifespan, how KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how vitamin D loss may contribute to age-related disease, and how they relate to mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that at least some of RAS-bl benefits in aging are mediated through the modulation of mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR actions in age retardation. Concluding, the available evidence endorses the idea that RAS-bl is among the interventions that may turn out to provide relief to the spreading issue of age-associated chronic disease. mechanistic target of rapamycin; vitamin D; caloric restriction; renin-angiotensin system EFFORTS AIMED AT DECIPHERING the mechanisms that underlie the aging process have unveiled three interventions that can increase survival and retard age-related diseases from lower organisms to mammals, i.e., caloric restriction (CR) (84,85,140,160,334), mechanistic target of rapamycin (mTOR; originally mammalian TOR) inhibition by rapamycin (173,196,281), and renin-angiotensin system blockade (RAS-bl) (20, 21, 26,63,253,284,354), although the latter has been less studied. In light of these findings, some intriguing questions come to mind: Do these interventions attenuate aging by interfering with common mechanisms? Do the mechanisms that are interfered with by CR, rapamycin, and RAS-bl mutually affect each other? Are there any pathways involved exclusively with a certain intervention?Previously (101), we have discussed the converging effects d...

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Section: Ras and Igf Signalingmentioning

confidence: 99%

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Cavanagh

Inserra

Ferder

2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In addition, anemia due to ACEIs and ARBs has been associated with reduced erythropoietin production as a result of increased oxygen supply via enhanced renal plasma flow. 27 ACEIs have been shown to lower insulin-like growth factor levels, 14,28 which are associated with erythroid stimulation, and to inhibit catabolism of N-acetyl-seryl-aspartyl-proline, a natural peptide that decreases proliferation of red cell precursors. 29 Clinical studies to assess the effects of ACEIs/ARBs on erythropoiesis have resulted in conflicting results.…”

Section: Changes In Hemoglobin After Treatment With Aceis and Arbsmentioning

confidence: 99%

Effects of the Renin-Angiotensin System Blockade on Hemoglobin Levels in Type 2 Diabetic Patients With Chronic Kidney Disease

Inoue

Babazono

Iwamoto

2008

American Journal of Hypertension

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“…One of these pathways, the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway, is activated by several cytokines and growth factors such as interleukin-12 and insulinlike growth factor-1. 49,50 This pathway may also be involved in the effect of Ang II on For personal use only. on May 10, 2018. by guest www.bloodjournal.org From erythropoietin synthesis in the kidney.…”

mentioning

confidence: 99%

Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo

Savary

Michaud

Favier

et al. 2005

Blood

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Inactivation of the gene encoding mouse angiotensin I-converting enzyme (ACE), which converts angiotensin I into angiotensin II, results in anemia in adult animals. This anemia is corrected by angiotensin II, demonstrating the involvement of angiotensin II in adult (definitive) erythropoiesis. We investigated the possible role of the renin-angiotensin system (RAS) in primitive erythropoiesis in the yolk sac of the chicken embryo. Enzymatically active ACE was detected in the yolk sac endoderm, concomitantly with the differentiation of blood islands in the adjacent yolk sac mesoderm. The simultaneous presence of all the other components of the RAS (renin, angiotensinogen, angiotensin II receptor) in the vicinity of the blood islands suggests that this system is involved in erythropoiesis. This role was confirmed by in vivo blockade of the RAS with fosinoprilate, a specific inhibitor of chicken ACE, which decreased hematocrit by 15%. A similar decrease in hematocrit was observed following treatment with the angiotensin II receptor antagonist Sar1-Ile8-Angiotensin II, suggesting that this effect was mediated by angiotensin II. Both treatments affected hematocrit by decreasing erythroblast proliferation. Thus, the RAS, and its effector peptide angiotensin II in particular, modulates primitive erythropoiesis. IntroductionAngiotensin I converting-enzyme (ACE) is a key element of the renin-angiotensin system (RAS), an integrated system of peptides, enzymes, and membrane receptors, the principal role of which is the regulation of blood pressure and hydromineral homeostasis. This function is accomplished by generation of the octapeptide angiotensin II (Ang II) from the inactive decapeptide angiotensin I (Ang I). 1 Ang II exerts a strong vasopressor effect, but evidence is accumulating that this molecule has several other important functions: it has been found to be proinflammatory, 2 to facilitate the generation of reactive oxygen species (ROS), 3 and to possess hypertrophic and hyperplastic properties in various cell types. [4][5][6][7] The RAS also appears to regulate hematopoiesis, in both experimental models and humans. Indeed, ACE knock-out mice present isolated normochrome anemia, 8 whereas in humans, anemia and leukopenia have been reported following the initiation of treatment with high doses of ACE inhibitors. 9,10 RAS blockade with Ang II receptor antagonists or ACE inhibitors has even been used to treat patients with posttransplantation erythrocytosis or polycythemia vera. 11,12 Finally, further indirect evidence for involvement of the RAS in hematopoiesis is provided by the marked increase in plasma renin concentration reported in patients with chronic obstructive pulmonary disease accompanied by secondary erythrocytosis, 13 suggesting a common causal relationship.This demonstration of a role for ACE in the regulation of adult hematopoiesis led us to investigate the possible role of this enzyme in another important hematopoietic event: primitive hematopoiesis. We used a simple and comprehensive model: the chi...

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Interference of Angiotensin-Converting Enzyme Inhibitors on Erythropoiesis in Kidney Transplant Recipients

Abstract: IGF-1 seems to play a role in the ACEI-related decrease of Hct in patients with PTE, chiefly in patients without any modification of EPO serum levels.

Cited by 77 publications

References 37 publications

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Effects of the Renin-Angiotensin System Blockade on Hemoglobin Levels in Type 2 Diabetic Patients With Chronic Kidney Disease

Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo

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