Bioprosthetic heart valves

a heart valve and bioprosthetic technology, applied in the field of bioprosthetic heart valves, can solve the problems of significant tissue calcification, high cost, and high cost, and achieve the effects of improving overall human health care, and reducing the risk of heart valve failur

Inactive Publication Date: 2006-02-23
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010] The invention also is based on the discovery that serotonin receptor antagonists (e.g., 5HT1B receptor antagonists) can inhibit serotonin-induced proliferation of heart valve cells from patients diagnosed with carcinoid heart disease. Thus, serotonin receptor antagonists can be used to treat carcinoid heart disease. Further, the methods and materials used to identify serotonin receptor antagonists as a treatment for carcinoid heart disease also can be used to identify drugs for the treatment of other valvular heart diseases as well as test the safety of any drug designed for human use. Clearly, identifying new valvular heart disease treatments and determining drug safety in general will greatly improve overall human health care.

Problems solved by technology

A heart valve can malfunction either by failing to open properly (stenosis) or by leaking (regurgitation).
Unfortunately, replacement valves are susceptible to problems such as degeneration, thrombosis, and calcification.
For example, significant expression of osteopontin, a polypeptide abundant in bone matrix, can lead to significant tissue calcification.
For example, significant proliferation and apoptosis of heart valve cells can lead to heart valve thickening, and thus heart valve malfunction and degeneration.

Method used

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Examples

Experimental program
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Effect test

example 1

Effects of Hyperlipidemia on Heart Valve Tissue

[0065] Rabbits were used since they have a propensity to develop endothelial dysfunction when subjected to a cholesterol diet. The effects of feeding New Zealand White Rabbits a diet supplemented with 1% cholesterol (wt / wt; Purina Mills, Woodmont, Ind.) were studied. Briefly, the rabbits were fed cholesterol for ten weeks, while control rabbits received a normal diet. After ten weeks, the rabbits were anesthetized using intramuscular ketamine (68 mg / kg), xylazine (9 mg / kg), and aceprmazine (2.3 mg / kg). Heparin (100 U / kg) was administered intracardially, and the rabbits were killed four to five minutes later with an overdose of a pentobarbital sodium solution. The thorax was opened widely, and the heart removed for histologic, RT-PCR, and immunostaining analysis of the aortic heart valve. After removal, the aortic heart valves were either frozen in liquid nitrogen, or fixed in 10% formalin and embedded in parafilm. The valvular appearan...

example 2

Effects of HMG CoA Reductase Inhibitors and Oxidative Stress on Heart Valve Tissue In Vitro

[0071] Valvular endothelial and subendothelial tissues were obtained from mature pigs and used to create primary explant cultures. Briefly, the cells were isolated from the cardiac aortic valves by collagenase digestion, and cultured in medium 199 with 10% (v / v) heat-inactivated fetal bovine serum at 37° C. in a humidified atmosphere of 5% CO2 in air. For each experiment, the cells were used between the 3rd and 7th passage. Cells were grown to about 80 percent confluence in 24-well plates. Once at about 80 percent confluence, the cells were incubated in serum-free medium for 24 hours to arrest growth. After the 24 hour incubation, LDL (10 μg / mL) alone, pravastatin (100 nM) alone, or LDL (10 μg / mL) plus pravastatin (100 nM) was added to the wells, and the cells incubated for 18 hours. Controls were cells treated with either serum-free media or media containing 10% fetal bovine serum. Pravastat...

example 3

Adenoviral Vectors

[0077] Adenoviral vectors containing a cDNA encoding either β-galactosidase or eNOS were constructed using methods similar to those described by Tsutsui et al. (Arterio. Thromb. Vascul. Biol. 18:1231-1241 (1998). Briefly, each vector was produced by cloning the cDNA of interest into a plasmid containing a subsegment of the adenoviral genome. Each resulting construct then was cotransfected into human E1a-293 cells along with adenoviral DNA containing an E1a deletion. Adenoviruses containing a E1a deletion are replication defective, however, viral replication can occur within E1a-293 cells since these cells provide E1a products in trans. Through homologous recombination, recombinant adenoviral vectors containing the cDNA of interest were produced within the 293 cells. The recombinant adenoviral vectors were isolated and propagated. Once collected, each adenoviral vector stock was stored at −70° C. in 0.01M Tris, 0.01M MgCl, and 10% glycerol. The recombinant adenovir...

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Abstract

The invention provides methods and materials related to heart valves and the treatment of valvular heart disease. Specifically, the invention provides non-murine heart valve cells and heart valve cusps as well as methods for making heart valves. The invention also provides methods and materials for (1) slowing heart valve degeneration, thrombosis, and calcification, (2) treating carcinoid heart disease, (3) identifying inhibitors of heart valve degeneration, thrombosis, and calcification, and (4) determining the safety of drugs.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional (and claims the benefit of priority under 35 USC 120) of U.S. application Ser. No. 10 / 667,625, filed Sep. 22, 2003, which is a divisional of U.S. application Ser. No. 09 / 399,704, filed Sep. 21, 1999, now U.S. Pat. No. 6,660,260.BACKGROUND [0002] 1. Technical Field [0003] The invention relates to bioprosthetic heart valves and the treatment of valvular heart disease. [0004] 2. Background Information [0005] The heart is a hollow, muscular organ that circulates blood throughout an animal's body by contracting rhythmically. In mammals, the heart has four-chambers situated such that the right atrium and ventricle are completely separated from the left atrium and ventricle. Normally, blood flows from systemic veins to the right atrium, and then to the right ventricle from which it is driven to the lungs via the pulmonary artery. Upon return from the lungs, the blood enters the left atrium, and then flows to th...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K48/00A61K31/5377A61K31/22A61K31/366A61K31/40A61K31/404A61K31/7052A61K35/12A61L27/36A61L27/38C12N5/071G01N33/50
CPCA61K31/22C12Y114/13039A61K31/40A61K31/404A61K31/5377A61K31/7052A61K38/44A61K48/005A61K48/0075A61L27/3625A61L27/3645A61L27/3683A61L27/3695A61L27/38A61L27/507C12N5/0602C12N15/86C12N2501/03C12N2501/70C12N2510/00C12N2710/10343G01N33/5008G01N33/5011G01N33/5061G01N33/5064G01N33/5088A61K31/366A61K2300/00
Inventor RAJAMANNAN, NALINI M.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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