INSULIN-LIKE GROWTH FACTOR 1: CARDIOVASCULAR MORBIDITY PROGNOSIS

2021 ◽  
pp. 6-17
Author(s):  
V.A. Razin ◽  
L.T. Nizamova ◽  
V.V. Gnoevykh ◽  
I.V. Razina ◽  
M.O. Zhdanova ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Growth Factor ◽  
Arterial Hypertension ◽  
Regulatory Function ◽  
Insulin Like Growth Factor ◽  
Coronary Syndrome ◽  
Igf I

The paper is a review devoted to insulin-like growth factor 1 and its role in the development, progression, and prognosis of cardiovascular diseases. IGF-I is one of the important regulatory proteins involved in both adaptation and maladjustment. The purpose of the review is to critically analyze the results of association between IGF-1 and cardiovascular disease. In general, we analyzed 100 literature sources; however, 49 of them were excluded, since the processes under consideration were not described there in detail or included an assessment of correlation between IGF-1 and metabolic parameters. IGF-I regulatory function is to control the synthesis and degradation of proteins, provide a mitogenic effect, and influence apoptosis. IGF-1 plays a leading role in the protection of cardiomyocytes from apoptosis both in vitro and in vivo. IGF-1 is involved in angiogenesis and development of atherosclerosis; it induces the growth of endothelial cells activating vascular endothelial growth factor. An increase in IGF-1 level accompanies arterial hypertension; a decrease in IGF-1 concentration is associated with an increased risk of coronary heart disease, stroke, and heart failure.IGF-1 concentration in ACS is associated with the syndrome outcome; a decrease in IGF-1 levels in patients with myocardial infarction (less than 150 nm/ml) is an unfavorable prognostic factor for six-month mortality after acute coronary pathology. Low IGF-1 level is an independent predictor of vascular accidents in hypertensive patients. Decreased IGF-1 level in patients with cardiovascular disease is associated with a higher risk of atrial fibrillation. The results obtained indicate the advisability of using the IGF-1 concentration as a prognostic marker of cardiovascular diseases. Key words: insulin-like growth factor, arterial hypertension, acute coronary syndrome, apoptosis, cardiovascular diseases, remodeling. Статья представляет собой обзор исследований, посвященных изучению роли инсулиноподобного фактора роста-1 в развитии, прогрессировании, прогнозе кардиоваскулярных заболеваний. IGF-I является одним из важных регуляторных белков, участвующих в процессах как адаптации, так и дезадаптации. Цель обзора – провести критический анализ результатов исследований взаимосвязи IGF-1 и сердечно-сосудистых заболеваний. Проанализировано 100 источников литературы, из них 49 источников исключены, так как интересующие процессы не были подробно описаны или включали оценку взаимосвязей IGF-1 с метаболическими параметрами. Регуляторная функция IGF-I заключается в регуляции синтеза и распада белков, оказании митогенного эффекта, влиянии на апоптоз. IGF-I играет ведущую роль в защите кардиомиоцитов от апоптоза как in vitro, так и in vivo. IGF-I принимает участие в развитии атеросклероза и в ангиогенезе, он индуцирует рост эндотелиальных клеток, участвуя в активации фактора роста эндотелия сосудов. Повышение уровня IGF-I сопровождает артериальную гипертензию, уменьшение концентрации IGF-I ассоциируется с повышенным риском развития ишемической болезни сердца, инсульта и сердечной недостаточности. Концентрация IGF-I при ОКС связана с исходом данного синдрома, снижение уровней IGF-I у пациентов с инфарктом миокарда (менее 150 нм/мл) является неблагоприятным прогностическим фактором полугодовой летальности после острой коронарной патологии. Низкий уровень IGF-1 – это независимый предиктор развития сосудистых катастроф у пациентов с артериальной гипертензией. Снижение уровня IGF-1 у пациентов с кардиоваскулярной патологией связано с более высоким риском развития фибрилляции предсердий. Полученные результаты свидетельствуют о целесообразности использования концентрации IGF-1 как прогностического маркера кардиоваскулярных заболеваний. Ключевые слова: инсулиноподобный фактор роста, артериальная гипертензия, острый коронарный синдром, апоптоз, сердечно-сосудистые заболевания, ремоделирование.

scholarly journals Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Growth Hormone and Insulin-Like Growth Factor: In Vivo and In Vitro Studies1

1999 ◽  
Vol 84 (11) ◽  
pp. 4172-4177 ◽  
Author(s):  
J. S. Moore ◽  
J. P. Monson ◽  
G. Kaltsas ◽  
P. Putignano ◽  
P. J. Wood ◽  
...  
Keyword(s):  
Growth Factor ◽  
Reductase Activity ◽  
Primary Cultures ◽  
Inverse Correlation ◽  
Hydroxysteroid Dehydrogenase ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Glucose Output

The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD), an oxo-reductase converting E to F (11βHSD1) and a dehydrogenase (11βHSD2) converting F to E. 11βHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11βHSD1 activity. In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20–40 mg/month for at least 12 months), GH rose from 7.1 ± 1.5 to 17.5 ± 4.3 mU/L (mean ± se), and insulin-like growth factor I (IGF-I) rose from 43.0 ± 8.8 to 82.1 ± 13.7 nmol/L (both P < 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 ± 0.06 to 0.60 ± 0.06; P < 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11βHSD2 activity) suggested that this was due to inhibition of 11βHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = −0.422; P < 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 ± 49.2 to 29.3 ± 15.4 mU/L; P < 0.01), the THF+allo-THF/THE ratio rose from 0.53 ± 0.06 to 0.63 ± 0.07 (P < 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio. In vitro studies conducted on cells stably transfected with either the human 11βHSD1 or 11βHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11βHSD1 isozyme indicated a dose-dependent inhibition of 11βHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11βHSD2 activity. GH, through an IGF-I-mediated effect, inhibits 11βHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11βHSD1 expression.

scholarly journals Viral expression of insulin-like growth factor I E-peptides increases skeletal muscle mass but at the expense of strength

2014 ◽  
Vol 306 (8) ◽  
pp. E965-E974 ◽  
Author(s):  
Becky K. Brisson ◽  
Janelle Spinazzola ◽  
SooHyun Park ◽  
Elisabeth R. Barton
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Muscle Mass ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) is a protein that regulates and promotes growth in skeletal muscle. The IGF-I precursor polypeptide contains a COOH-terminal extension called the E-peptide. Alternative splicing in the rodent produces two isoforms, IA and IB, where the mature IGF-I in both isoforms is identical yet the E-peptides, EA and EB, share less than 50% homology. Recent in vitro studies show that the E-peptides can enhance IGF-I signaling, leading to increased myoblast cell proliferation and migration. To determine the significance of these actions in vivo and to evaluate if they are physiologically beneficial, EA and EB were expressed in murine skeletal muscle via viral vectors. The viral constructs ensured production of E-peptides without the influence of additional IGF-I through an inactivating mutation in mature IGF-I. E-peptide expression altered ERK1/2 and Akt phosphorylation and increased satellite cell proliferation. EB expression resulted in significant muscle hypertrophy that was IGF-I receptor dependent. However, the increased mass was associated with a loss of muscle strength. EA and EB have similar effects in skeletal muscle signaling and on satellite cells, but EB is more potent at increasing muscle mass. Although sustained EB expression may drive hypertrophy, there are significant physiological consequences for muscle.

scholarly journals Separation of Fast from Slow Anabolism by Site-specific PEGylation of Insulin-like Growth Factor I (IGF-I)

2011 ◽  
Vol 286 (22) ◽  
pp. 19501-19510 ◽  
Author(s):  
Friedrich Metzger ◽  
Waseem Sajid ◽  
Stefanie Saenger ◽  
Christian Staudenmaier ◽  
Chris van der Poel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Site Specific ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) has important anabolic and homeostatic functions in tissues like skeletal muscle, and a decline in circulating levels is linked with catabolic conditions. Whereas IGF-I therapies for musculoskeletal disorders have been postulated, dosing issues and disruptions of the homeostasis have so far precluded clinical application. We have developed a novel IGF-I variant by site-specific addition of polyethylene glycol (PEG) to lysine 68 (PEG-IGF-I). In vitro, this modification decreased the affinity for the IGF-I and insulin receptors, presumably through decreased association rates, and slowed down the association to IGF-I-binding proteins, selectively limiting fast but maintaining sustained anabolic activity. Desirable in vivo effects of PEG-IGF-I included increased half-life and recruitment of IGF-binding proteins, thereby reducing risk of hypoglycemia. PEG-IGF-I was equipotent to IGF-I in ameliorating contraction-induced muscle injury in vivo without affecting muscle metabolism as IGF-I did. The data provide an important step in understanding the differences of IGF-I and insulin receptor contribution to the in vivo activity of IGF-I. In addition, PEG-IGF-I presents an innovative concept for IGF-I therapy in diseases with indicated muscle dysfunction.

scholarly journals Roles of erythropoietin, insulin-like growth factor 1, and unidentified serum factors in promoting maturation of purified murine erythroid colony-forming units

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2503-2512 ◽  
Author(s):  
SH Boyer ◽  
TR Bishop ◽  
OC Rogers ◽  
AN Noyes ◽  
LP Frelin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Degradation ◽  
Insulin Like Growth Factor ◽  
Serum Factor ◽  
Serum Factors ◽  
Factor I ◽  
Colony Forming Units ◽  
Igf I

We have used 75% to 90% pure murine erythroid colony-forming units (CFU- E) to delineate the processes and factors underlying their maturation. These CFU-E form 32 cell colonies and are drawn from what we term generation I of a six-generation long maturation sequence (Landschulz et al, Blood 79:2749, 1992). Applying assays of 59Fe-heme biosynthesis and colony numbers as measures of maturation and analyses of DNA degradation as an index of programmed cell death, we find that (1) erythropoietin (Epo) enhances maturation throughout most of its course; (2) Epo first seems able to forestall DNA degradation when CFU-E reach generation II; (3) the processes that Epo elicits thereafter start to persist when Epo is withdrawn; (4) insulin-like growth factor I (IGF-I) also forestalls DNA breakdown, but later loses effectiveness; (5) IGF-I adds little to maturation when Epo levels are high, but when Epo levels are low, enhances it substantially; and (6) for maturation to be entirely optimal, an unidentified serum factor(s) is probably required when Epo levels are high and is certainly needed when Epo levels are like those in normal animals. Quantitatively, about 40% of optimal in vitro erythropoiesis at normal Epo levels depends on Epo alone, another 30% or less on the addition of IGF-I, and the remaining 30% or more on the addition of unidentified serum factor(s). Applied together, these three or more factors lead to two-thirds of the maximum maturation realized with saturating Epo levels. Because we also find that heme accumulated in CFU-E culture can closely approach levels in red blood cells, we suppose that our conclusions apply as well to CFU-E maturation in vivo.

In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats

Bone ◽  
1994 ◽  
Vol 15 (6) ◽  
pp. 647-653 ◽  
Author(s):  
H. Tanaka ◽  
R. Quarto ◽  
S. Williams ◽  
J. Barnes ◽  
C.T. Liang
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Old Rats ◽  
Growth Factor I ◽  
In Vitro Effects

scholarly journals Roles of erythropoietin, insulin-like growth factor 1, and unidentified serum factors in promoting maturation of purified murine erythroid colony-forming units

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2503-2512 ◽  
Author(s):  
SH Boyer ◽  
TR Bishop ◽  
OC Rogers ◽  
AN Noyes ◽  
LP Frelin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Degradation ◽  
Insulin Like Growth Factor ◽  
Serum Factor ◽  
Serum Factors ◽  
Factor I ◽  
Colony Forming Units ◽  
Igf I

Abstract We have used 75% to 90% pure murine erythroid colony-forming units (CFU- E) to delineate the processes and factors underlying their maturation. These CFU-E form 32 cell colonies and are drawn from what we term generation I of a six-generation long maturation sequence (Landschulz et al, Blood 79:2749, 1992). Applying assays of 59Fe-heme biosynthesis and colony numbers as measures of maturation and analyses of DNA degradation as an index of programmed cell death, we find that (1) erythropoietin (Epo) enhances maturation throughout most of its course; (2) Epo first seems able to forestall DNA degradation when CFU-E reach generation II; (3) the processes that Epo elicits thereafter start to persist when Epo is withdrawn; (4) insulin-like growth factor I (IGF-I) also forestalls DNA breakdown, but later loses effectiveness; (5) IGF-I adds little to maturation when Epo levels are high, but when Epo levels are low, enhances it substantially; and (6) for maturation to be entirely optimal, an unidentified serum factor(s) is probably required when Epo levels are high and is certainly needed when Epo levels are like those in normal animals. Quantitatively, about 40% of optimal in vitro erythropoiesis at normal Epo levels depends on Epo alone, another 30% or less on the addition of IGF-I, and the remaining 30% or more on the addition of unidentified serum factor(s). Applied together, these three or more factors lead to two-thirds of the maximum maturation realized with saturating Epo levels. Because we also find that heme accumulated in CFU-E culture can closely approach levels in red blood cells, we suppose that our conclusions apply as well to CFU-E maturation in vivo.

From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass

2003 ◽  
Vol 228 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Shoshana Yakar ◽  
Clifford J. Rosen
Keyword(s):  
Growth Factor ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Insulin Like Growth Factor ◽  
In Vivo Models ◽  
Igf I

The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the “somatomedin hypothesis” in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

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