Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0264733 (
ventricular dilatation
)
2,163
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recently,
PSEN1
has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of
PSEN1
in cardiomyopathy remains unresolved. Here, we established four types of genetically modified mice to determine the function of
PSEN1
in cardiac development and pathology.
PSEN1
null mutation resulted in perinatal death, retardation of heart growth,
ventricular dilatation
, septum defects, and valvular thickening.
PSEN1
knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes. Cardiovascular loss of function of
PSEN1
induced by Sm22a-Cre or Myh6-Cre/ER/tamoxifen also resulted in severe ultrastructural abnormalities, such as relaxed gap junctions between neighboring cardiomyocytes. Functionally, cardiovascular deletion of
PSEN1
caused spontaneous mortality from birth to adulthood and led to diastolic heart dysfunction, including decreased volume of the left ventricle at the end-systolic and end-diastolic stages. Additionally, in a myocardial ischemia model, deletion of
PSEN1
in the cardiovascular system first protected mice by inducing adaptive hypertrophy but ultimately resulted in severe heart failure. Furthermore, a collection of genes was abnormally expressed in the hearts of cardiac-specific
PSEN1
knockout mice. They were enriched in cell proliferation, calcium regulation, and so on. Taken together, dynamic regulation and abnormal function of
PSEN1
underlie the pathogenesis of cardiovascular diseases due to ultrastructural abnormality of cardiomyocytes.
...
PMID:Conditionally targeted deletion of PSEN1 leads to diastolic heart dysfunction. 2861 69
