葦の髄から循環器の世界をのぞく

循環器関連の学会で血中IGF-1測定の発表があり気になったのでちょっと調べてみました。
ここ７〜８年前から心不全の指標として、また難治性心不全や拡張型心筋症（DCM）の治療薬として臨床応用が模索されているようです。
また抗老化作用や筋力増加作用（ドーピングにひっかかりにくい？）を期待しての話題もあるようです。

このIGF-I(Insulin like growth factors)はソマトメジンCとも呼ばれる70個のアミノ酸からなる単鎖ポリペプチドで,骨及び体細胞における成長ホルモン(GH)の成長促進作用を仲介する因子のひとつです。

IGF-1には、怪我や病気で損傷を受けた末梢神経組織を修復する働きがあることも分かりました。
PDGF(血小板由来成長因子)などのような他の成長因子とIGF-1とを組合せて使用すると、傷ついた組織が劇的に再生されました。また、動物や培養細胞実験では、脊髄の中で運動能力を管理するニューロンの活動をIGF-1が活発化することも判明しました。

もしIGF-1が脊髄の運動ニューロンを再生できるのなら、治療不可能だと言われている筋萎縮性側策硬化症(ALS)などの難病の治療に使用できる、と確信している研究者もいます。

循環器領域におけるIGF-1の研究は将来性があるのでしょうか。
診断法や治療法として臨床応用はされるようになるのでしょうか。
今ひとつ分かりません。

遺伝子ドーピング
http://www.nikkei-bookdirect.com/science/page/magazine/0409/doping.html
スポ-ツ界に新たな誘惑／成長ホルモン「ＩＧＦ1」
http://cliplife.jp/clip/?content_id=mwhv6qba

村山俊夫　油絵８号「白樺晩秋」１９７２年制作
http://page15.auctions.yahoo.co.jp/jp/auction/t49212407

Increased level of pericardial insulin-like growth factor-1 in patients with left ventricular dysfunction and advanced heart failure.
Abe N, et al
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.

OBJECTIVES:
To test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients.

BACKGROUND:
Local IGF-1 systems are regulated differently from the systemic IGF-1 system.
The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure.

METHODS:
We measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity.
The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function.

　中　略

CONCLUSIONS:
The pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.

PMID: 17010800 [PubMed - indexed for MEDLINE]

Abe N,ｅｔ　ａｌ

Increased level of pericardial insulin-like growth factor-1 in patients with left ventricular dysfunction and advanced heart failure. J Am Coll Cardiol 2006;48:1387-1395
http://www.ncbi.nlm.nih.gov/sites/entrez

Growth hormone treatment in dilated cardiomyopathy.
Perrot A et al.
Treatment with human recombinant growth hormone (GH) has yielded conflicting results in patients with congestive heart failure. We analyzed the baseline somatotrophic axis in 50 patients with dilated cardiomyopathy. Then, a double-blind, randomized, placebo-controlled study of GH was performed. We randomly allocated these patients to treatment with subcutaneous GH (2 IU daily) or placebo for a minimum of 12 weeks. The primary end-points were the effect on left ventricular (LV) mass and systolic wall stress. The secondary endpoint was LV ejection fraction. Severity of heart failure as determined by cardiac index, LV end-diastolic diameter, and plasma noradrenaline concentrations correlated markedly with baseline serum insulin-like growth factor-1 (IGF-1) levels.

　中略

There is a marked increase in LV mass in patients with dilated cardiomyopathy given GH. Changes in LV mass are related to changes in serum IGF-1 concentrations.
PMID: 11766830 [PubMed - indexed for MEDLINE]
Growth hormone treatment in dilated cardiomyopathy.
J Card Surg. 2001 Mar-Apr;16(2):127-31.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&

TermToSearch=11766830&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_

ResultsPanel.Pubmed_RVAbstractPlus

Role of growth hormone in chronic heart failure. Therapeutic implications.
Volterrani M, Manelli F, Cicoira M, Lorusso R, Giustina A.
Fondazione S. Maugeri, Cardiology Department, Gussago Medical Centre, Brescia, Italy. mvolterrani@fsm.it

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.
PMID: 11085197 [PubMed - indexed for MEDLINE]

Drugs. 2000 Oct;60(4):711-9.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&Term

ToSearch=11085197&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.

Pubmed_RVAbstractPlus

 (総説的な内容です。)

IGF-1(インシュリン成長因子-1)
http://www.google.co.jp/search?q=IGF-1&hl=

ja&lr=&start=10&sa=N
(IGF-1の抗老化作用としての可能性について述べられています。）
IGF-１ (ソマトメジンC)
http://www.srl.info/srlinfo/kensa_ref_CD/KENSA/SRL0752.htm

CASEーJ座談会
慢性心不全の治療と、予防への展開
http://www.case-j.com/pdf/070514/expert_meeting.pdf
●心肥大に関与する液性因子としては、Ang IIやエンドセリ
ン-1などの血管作動物質、ノルエピネフリンを代表とする神
経因子、カルジオトロフィン1、白血病抑制因子（LIF）など
のサイトカイン、さらにインスリン、IGF-1、bFGFなどの細
胞増殖因子が心肥大の誘因となることが報告されています。
●まだクリアには分けられませんが、生理的肥大に
は主にインスリン、IGF-1、PI3K-Akt経路のシグナルが働
き、病的肥大にはAng Iによる7回膜貫通型受容体を介し
たシグナルが主に働いている、と考えられます。ただし、
病的肥大と生理的肥大についての明確な定義はまだありま
せんし、必ずしもクリアに分けられるものではない、と考
えています。