Serum Endostatin in the Coronary Circulation of Patients With Coronary Heart Disease and Its Relation to Coronary Collateral Formation

Mitsuma, Wataru; Kodama, Makoto; Hanawa, Haruo; Ito, Masahiro; Ramadan, Mahmoud M.; Hirono, Shuichi; Obata, Hiroaki; Okada, Shinsuke; Sanada, Fumihiro; Yanagawa, Takao; Kashimura, Takeshi; Fuse, Koichi; Tanabe, Naohito; Aizawa, Yoshifusa

doi:10.1016/j.amjcard.2006.09.095

Cited by 54 publications

(56 citation statements)

References 19 publications

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“…Finally, we cannot yet define the tissue source or target of circulating ES. Although it is clear that circulating ES can be produced by the human heart in cardiovascular disease (14)(15)(16), it remains to be determined if this is the case in PAH. Our unpublished data indicate that Col18a1 mRNA and ES protein are selectively upregulated in the RV, not the left ventricle, in preclinical models of pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…In ischemic heart disease, elevated ES levels in the circulation, pericardial space, and myocardial tissue have been associated with diminished collateral circulation within the heart (14)(15)(16). These small studies in humans with left heart disease indicate that the myocardium is a source of serum ES, which can be detected in the peripheral circulation (14).…”

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confidence: 99%

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Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Damico

Kolb

Valera

et al. 2015

Am J Respir Crit Care Med

102

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Rationale: Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH.Objectives: We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH.Methods: We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minutewalk distance, invasive hemodynamics, and laboratory chemistries.Measurements and Main Results: Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality.Conclusions: Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Damico

Kolb

Valera

et al. 2015

Am J Respir Crit Care Med

102

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“…4,22 Mechanical stretch of the vasculature, as seen in hypertension, induces vascular extracellular remodeling by activation of metalloproteinase-2 and metalloproteinase-9, 23 which both are proteases that play an important role in the degradation of collagen XVIII to endostatin. Moreover, experimental studies show that damages to the vasculature, 24 the myocardium, 25 and the kidneys 26 lead to increased expression of endostatin in these tissues, and that circulating concentrations of endostatin are elevated in patients with prevalent cardiovascular diseases 20,[27][28][29][30] or chronic kidney disease. 13 Thus, the fact that endostatin was both associated with the duration of hypertension and indices of vascular, myocardial, and renal hypertensive target-organ damage in the present study may indicate that higher circulating levels of endostatin mirror an increased extracellular remodeling that originates from these tissues.…”

Section: Discussionmentioning

confidence: 99%

Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage

et al. 2013

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Abstract-Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive targetorgan damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001).In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage.

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“…Especially, the elderly appeared to have high serum endostatin levels in the absence of CRC. The mechanism of such age-related increase in endostatin levels is unknown, but it might be associated with age-related increase in cardiovascular disease and the elevated endostatin levels in these patients (Mitsuma et al, 2007;Carlsson et al, 2013). Li et al, 2012 have reported that increased serum endostatin levels correlate with CRC progression.…”

Section: Discussionmentioning

confidence: 99%

172: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

Tuomisto¹,

Kantola²,

Väyrynen³

et al. 2014

European Journal of Cancer

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Serum Endostatin in the Coronary Circulation of Patients With Coronary Heart Disease and Its Relation to Coronary Collateral Formation

Cited by 54 publications

References 19 publications

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage

172: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

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