Assessing left ventricular remodeling via temporal detection and measurement of microRNA in body fluids
Inventors
Spinale, Francis G. • Zile, Michael R. • Stroud, Robert E.
Assignees
MUSC Foundation for Research and Development • US Department of Veterans Affairs
Publication Number
US-8592151-B2
Publication Date
2013-11-26
Expiration Date
2030-11-11
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Abstract
Disclosed are methods and materials for assessing cardiac failure, cardiac hypertrophy, and left ventricular remodeling using microRNA levels. The level of microRNAs can be measured in a body fluid, such as plasma and serum.
Core Innovation
Disclosed are methods and materials for assessing cardiac failure, cardiac hypertrophy, and left ventricular remodeling using microRNA levels. The level of microRNAs can be measured in a body fluid, such as plasma and serum, at a plurality of different times. The temporal pattern of the level of one or more target microRNAs indicates the presence, severity, or a combination of left ventricular remodeling in the subject, which can be compared to one or more reference temporal patterns.
MicroRNAs relevant to cardiac disease, including left ventricular remodeling, can be reliably measured in body fluids like plasma and serum. The levels of these microRNAs follow temporal patterns after myocardial infarction and during remodeling, and these temporal patterns are highly correlated to the severity of left ventricular remodeling. Thus, the disclosed invention addresses the detection of temporal changes in microRNA levels as indicators of myocardial infarction and left ventricular remodeling.
Claims Coverage
The patent includes one independent claim covering a method of detecting microRNAs over multiple time points to assess left ventricular remodeling.
Temporal detection of microRNAs for assessing left ventricular remodeling
A method comprising detecting one or more target microRNAs in a body fluid of a subject at multiple different times, wherein the temporal pattern of the level of these microRNAs indicates the presence, severity, or a combination of left ventricular remodeling in the subject.
Comparative analysis of temporal microRNA patterns to references
Indicating the presence, severity, or combination of left ventricular remodeling by comparing the temporal pattern of microRNA levels in the subject to one or more reference temporal patterns.
Use of specific microRNAs as targets
The one or more microRNAs used comprise one or more selected from groups including miR-1, miR-21, miR-23a, miR-29a, miR-30, miR-133a, miR-150, miR-195, miR-199, miR-208, miR-214, and miR-125b, or subsets thereof.
Body fluid sampling and timing for microRNA measurement
Measuring microRNAs in body fluids such as plasma, serum, blood, or lymphatic fluid, at two or more times separated by specified periods ranging from 1 up to 90 days, particularly following known or suspected myocardial infarction.
Normalization and expression of microRNA levels
Expressing the level of target microRNAs normalized to a reference RNA in the body fluid, such as snRNA U6, and expressing levels as fold differences compared to a reference subject measured at the same or different times.
Detection of myocardial infarction timing
Using the temporal pattern of microRNA levels to indicate that a subject suffered a myocardial infarction and determining how long ago it occurred.
The independent claim covers a method of temporally detecting specific microRNAs in body fluids to indicate left ventricular remodeling and myocardial infarction presence and timing, with normalization to reference RNAs and comparisons to reference temporal patterns.
Stated Advantages
Enables sensitive, reliable measurement of microRNAs in body fluids for assessment of cardiac remodeling.
Allows serial or temporal profiling of microRNA levels to diagnose and monitor left ventricular remodeling and myocardial infarction.
Correlates temporal microRNA patterns with severity of left ventricular remodeling, providing prognostic significance.
Documented Applications
Assessing, diagnosing, and monitoring cardiac failure, cardiac hypertrophy, and left ventricular remodeling in subjects.
Determining if and when a myocardial infarction occurred in a subject.
Diagnosing and distinguishing left ventricular hypertrophy versus diastolic heart failure.
Assessing and gaining mechanistic insights into thoracic aortic aneurysm disease.
Measuring microRNA dynamics in human myocardial interstitium after ischemia-reperfusion injury.
Studying microRNA expression regulation in human myocardial fibroblasts under electrical stimulation.
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