Van Eyk, Dunn - Proteomic and Genomic Analysis of Cardiovascular Disease - 2003 (522919), страница 17
Текст из файла (страница 17)
N. Y. Acad. Sci. 1998, 853, 329–332.Sack, M. N., Disch, D. L., Rockman,H. A., Kelly, D. P. A role for Sp and nuclear receptor transcription factors in acardiac hypertrophic growth program.Proc. Natl. Acad. Sci. USA. 1997, 94,6438–6443.Crie, J. S., Morton, P., Wildenthal, K.Changes in cardiac cathepsin B activityin response to interventions that alterheart size or protein metabolism: comparison with cathepsin D.
J. Mol. Cell.Cardiol. 1983, 15, 487–494.Li, J., Yen, C., Liaw, D., Podsypanina,K., Bose, S., et al. PTEN, a putative protein tyrosine phosphatase gene mutatedin human brain, breast, and prostate cancer . Science. 1997, 275, 1943–1947.Li, D. M., Sun, H. TEP1, encoded by acandidate tumor suppressor locus, is anovel protein tyrosine phosphatase regulated by transforming growth factor beta.Cancer Res. 1997, 57, 2124–2129.Steck, P. A., Pershouse, M. A., Jasser, S.A., Yung, W. K., Lin, H., et al. Identification of a candidate tumour suppressorgene, MMAC1, at chromosome 10q23.3that is mutated in multiple advancedcancers. Nat.
Genet. 1997, 15, 356–362.60616263646566676869Podsypanina, K., Ellenson, L. H.,Nemes, A., Gu, J., Tamura, M., et al. Mutation of Pten/Mmac1 in mice causesneoplasia in multiple organ systems.Proc. Natl. Acad. Sci. USA. 1999, 96,1563–1568.Stambolic, V., Suzuki, A., de la Pompa,J. L., Brothers, G.
M., Mirtsos, C., et al.Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998, 95, 29–39.Di Cristofano, A., Pesce, B., CordonCardo, C., Pandolfi, P. P. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 1998, 19,348–355.Myers, M. P., Stolarov, J. P., Eng, C.,Li, J., Wang, S. I., et al.
PTEN, the tumorsuppressor from human chromosome10q23, is a dual- specificity phosphatase.Proc. Natl. Acad. Sci. USA. 1997, 94,9052–9057.Kandel, E. S., Hay, N. The regulationand activities of the multifunctional serine/threonine kinase Akt/PKB. Exp. CellRes. 1999, 253, 210–229.Goberdhan, D.
C., Paricio, N., Goodman, E. C., Mlodzik, M., Wilson, C.Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 1999, 13, 3244–3258.Huang, H., Potter, C. J., Tao, W., Li,D. M., Brogiolo, W., et al. PTEN affectscell size, cell proliferation and apoptosisduring Drosophila eye development. Development. 1999, 126, 5365–5372.Ogg, S., Ruvkun, G. The C. elegansPTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signalingpathway.
Mol. Cell. 1998, 2, 887–893.Bhattacharjee, A., Richards, W. G.,Staunton, J., Li, C., Monti, S., et al.Classification of human lung carcinomasby mRNA expression profiling revealsdistinct adenocarcinoma subclasses. Proc.Natl. Acad. Sci. USA. 2001, 98, 13790–13795.Hanash, S. M., Bobek, M. P., Rickman,D. S., Williams, T., Rouillard, J.
M., etal. Integrating cancer genomics and proteomics in the post-genome era. Proteomics. 2002, 2, 69–75.43442 Cardiac Disease and The Transcriptome70Hughes, T. R., Marton, M. J., Jones,A. R., Roberts, C. J., Stoughton, R., etal. Functional discovery via a compendium of expression profiles. Cell. 2000,102, 109–126.71 Carrier, L., Bonne, G., Bahrend, E.,Yu, B., Richard, P., et al.
Organizationand sequence of human cardiac myosinbinding protein C gene (MYBPC3) andidentification of mutations predicted toproduce truncated proteins in familialhypertrophic cardiomyopathy. Circ. Res.1997, 80, 427–434.453Heart Failure: A Genomics ApproachChoong Chin Liew3.1Overview of Heart FailureHeart failure is a syndrome that occurs over time as the heart becomes less andless able to pump blood at a rate that is sufficient to meet the requirements ofthe body’s organs, tissues and cells.
For example, cardiomyopathies, which are disorders affecting the heart muscle, are a predominant cause of heart failure [1].Heart failure may be right sided, left-sided, systolic or diastolic, or both. Clinically,systolic heart failure, an impairment of the right ventricle’s ability to eject adequately during systole, is characterized by poor exercise tolerance and easy fatigability – characteristic effects of inadequate cardiac output and impaired tissueperfusion.
Diastolic heart failure, the inability of the left ventricle to fill normally,is characterized by dyspnea, orthopnea, hepatomegaly, ascites, and edema, whichresult from elevated venous pressure. Clinical severity of heart failure varies frommild and asymptomatic to disabling to fatal without heart assist or heart transplant.Congestive heart failure is rare in patients less than fifty; its prevalence increases to 5% for patients aged 50–70 and may be as high as 15% for patientsaged over eighty.
Heart failure is twice as common in black than in white populations and black patients tend to develop symptoms at a younger age [2]. Currentdrug therapies for heart failure include angiotensin-converting enzyme inhibitors,beta adrenergic blockers, diuretics and digoxin. However treatment success remains modest; patients with heart failure are often disabled, and survival is decreased. Having a diagnosis of heart failure increases the risk of death approximately four times, 5-year survival rates are 50% overall with median survival of1.7–3.1 years in men and women, respectively.
The likelihood of survival decreases with age and with more advanced heart failure [3].A significant and increasing cause of morbidity and mortality, heart failure isbecoming a major heath care burden. Over the past two decades the conditionhas increased by more than 150% and will continue to increase as the populationages and as death rates from acute myocardial infarction decline [2]. Currently,about 4 to 5 million people in the United States suffer from heart failure, resulting in the hospitalization of two million patients each year [4].
ApproximatelyProteomic and Genomic Analysis of Cardiovascular Disease.Edited by Jennifer E. van Eyk, Michael J. DunnCopyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimISBN: 3-527-30596-3463 Heart Failure: A Genomics Approach400,000 new cases of heart failure are diagnosed annually, and the cost of treatment is estimated at a low of US $10 billion annually [5], to as high as US $21 to$50 billion per year [2].
Life threatening heart failure unresponsive to drug therapy may require assistive devices, or heart transplant.Clearly the burden of heart failure in ill health and mortality, its high cost andincreasing prevalence are making it essential to develop new strategies for treating or preventing this common and debilitating disorder.
Our understanding ofheart failure is undergoing a paradigm shift as molecular, cellular and genetic research is developing new insights into the causes and progression of hypertrophyand heart failure. One result of this shift in thinking about heart failure is thatdrug therapies are beginning to be targeted to interfere in the progression of remodeling and improving contractility, rather than at symptom relief, as has beenthe approach in the past. Concurrent with advances at the molecular and cellularlevel, the genomics revolution is providing exciting new vistas of research to aidin further developing understanding of heart failure at the genomic level of genegene interactions and pathways.
Although such research is in its infancy and practical genomics-based therapies remain in the far distant future, genomic researchis beginning to provide new means to explore the extraordinary complexity of thegenetic webs and pathways of this disease.3.2Pathophysiology of Heart FailureA complex, multifactorial condition, heart failure occurs as a result of the interaction of environmental, physiological and genetic factors.
In the United States, coronary artery disease and scarring from myocardial infarction are the most common factors leading to heart failure, followed by cardiomyopathy, and hypertension. Heart failure can also occur in patients with valvular heart disease or sustained arrhythmia, or it may be secondary to toxic agents such as alcohol, somechemotherapeutic drugs, or to pulmonary or systemic diseases.
Regardless of theinitial insult, however, heart failure is the final common pathway of almost anydisease or injury that cause cardiac cell and tissue damage (Fig. 3.1).Over the past twenty years our understanding of the pathophysiology of heartfailure has undergone significant changes. The relatively simple hemodynamicmodel in which heart failure was regarded as a disorder of myocardial contractility has largely been superceded. Research efforts have reconceptualized the failingheart as much a condition of extracardiac neuroendocrine activation, cytokine release, and homeostatic mechanisms as it is a disorder of the heart proper [6].
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
