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Means and methods for diagnosing and/or treating a subject at risk of developing heart failure

A technology for heart failure and risk, applied in the fields of medicine and cardiology, can solve problems such as the inability to predict the outcome of heart failure and the inability to reliably prove heart failure

Inactive Publication Date: 2009-09-23
MAASTRICHT UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Current methods can reliably rule out actual heart failure, but cannot reliably demonstrate the presence of heart failure, nor can these methods predict the outcome of established heart failure, or predict the occurrence of heart failure

Method used

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  • Means and methods for diagnosing and/or treating a subject at risk of developing heart failure
  • Means and methods for diagnosing and/or treating a subject at risk of developing heart failure
  • Means and methods for diagnosing and/or treating a subject at risk of developing heart failure

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0057] Lysosomal integral membrane protein-2 is a new component of intercalary disc and prevents cardiomyopathy

[0058] Materials and methods

[0059] Ren-2 rat, microarray analysis and western blot

[0060] As mentioned earlier (Van Haaften et al., 2006), from ten-week-old Ren-2, Sprague-Dawley (SD) rats ( , Lille Skensveld, Denmark) took out a biopsy of LV. At 10 weeks, 12 weeks, 15 weeks, 16 weeks, 18 weeks, 19 weeks, and 21 weeks of age, the rats were subjected to continuous echocardiography. When the rats showed clinical signs of heart failure (heart failure tendency / HF Rats were sacrificed at 15 to 18 weeks when they were prone to rats); or when there were no clinical signs of exhaustion (compensated / comp rats), the rats were sacrificed at 21 weeks. As described earlier (Schroen et al., 2004; Heymans et al., 2005), total RNA was isolated from the LV biopsy and amplified, and the total RNA was hybridized to the Affymetrix rat 2302.0 gene chip and analyzed with Microarray ...

example 2

[0101] TGFβ promotes cardiac hypertrophy by inhibiting Krüppel-like factor 15, Krüppel-like factor 15 Is a new type of inhibitor of cardiac hypertrophy

[0102] Materials and methods

[0103] Transgenic rats, left ventricular biopsy and hemodynamic study

[0104] Eighteen male homozygous Ren-2 rats and five age-matched Sprague-Dawley (SD) ( Breeding Center, Lille Skensveld, Denmark). Three Ren-2 rats with clinical signs of heart failure were sacrificed at 10 to 12 weeks of age, and these three rats were excluded from the study. As mentioned earlier, at 10 weeks of age, biopsies of the left ventricle were taken from the remaining healthy 15 Ren-2 rats and 5 SD control rats. As described above, rats were subjected to continuous echocardiography at 10 weeks, 12 weeks, 15 weeks, 16 weeks, 18 weeks, 19 weeks, and 21 weeks of age. Nine Ren-2 rats with clinical signs of heart failure were sacrificed at 15 to 18 weeks of age and were designated as "prone to heart failure" rats. The r...

example 3

[0145] Krüppel-like factor 15, a transcription inhibitor of cardiac hypertrophy

[0146] According to the present invention, it has been shown that the zinc finger transcription factor Krüppel-like factor 15 (KLF-15) is an effective LV hypertrophy transcription inhibitor. Gene targeting studies have shown that KLF-15-deficient mice develop normally, but in response to pressure overload, they develop an expanded form of cardiac hypertrophy, which is characterized by increased heart weight, increased expression of hypertrophic genes, and increased muscle cell size. The left ventricular cavity dilates and the systolic function of the left ventricle decreases. In summary, these studies confirmed the role of KLF-15 in LV hypertrophy in vivo.

[0147] Interestingly, KLF-15 is down-regulated in several forms of pathological hypertrophy, but not in physiological hypertrophy, which means that KLF-15 is a regulator of pathological hypertrophy, not a regulator of physiological hypertrophy. ...

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Abstract

The present invention relates to a method for identifying a subject at risk of developing heart failure, comprising: (a) determining the level of one or more biological markers in a biological sample of said subject; (b) comparing the level of said biological marker to a standard level of the same biological marker; and (C) determining whether the level of the marker is indicative of a risk for developing heart failure, wherein the biological marker is Kruppel Like Factor 15 (KLF-15) and / or lysosomal integral membrane protein-2 (LIMP-2) and / or fragments and / or variants thereof, and / or wherein the biological marker is a gene coding for KLF15 and / or LIMP-2, and / or fragments and / or variants thereof. The invention further relates to use of the KLF15 and / or LIMP-2 protein, and / or the gene coding for KLF15 and / or LIMP2, and / or fragments, and / or variants of said genes and / or proteins, for the preparation of a medicament for a prophylactic and / or a therapeutic medicament for prevention and / or treatment of heart failure.

Description

Technical field [0001] The present invention generally relates to the field of medicine, and more specifically, the present invention relates to the field of cardiology. The present invention specifically relates to a device and method for diagnosing and / or treating subjects who are at risk of developing heart failure. Background technique [0002] It is well known that chronic heart load that occurs during long-term hypertension, valvular disease or other chronic diseases such as diabetes leads to cardiac hypertrophy, which is one of the most important risk factors for heart failure. Congestive heart failure (HF) is a common, serious and complex clinical syndrome, especially common in the elderly. Congestive heart failure is characterized by hyposystolic function and decreased exercise endurance. Symptoms of heart failure also include pulmonary and peripheral edema, fatigue and / or dyspnea. Because other organs cannot receive enough blood, severe heart failure can also cause the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68A61K38/16
Inventor 伊佳尔·M·品托埃丝特·E·克里梅斯朱斯特·L·林德斯
Owner MAASTRICHT UNIVERSITY