Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment.

Background: It is known that 5-lipoxygenase and its product, leukotriene B4 (LTB4), are highly expressed in several human pathologies, including atherosclerotic plaque. LTB(4) signals primarily through its high-affinity G protein-coupled receptor BLT1, which is expressed on specific leukocyte subsets. BLT1 receptor expression and function on other atheroma-associated cell types is unknown.

Heart valve regeneration.

The valves of the heart cannot regenerate spontaneously. Therefore, heart valve disease generally necessitates surgical repair or replacement of the diseased tissue by mechanical or bioprosthetic valve substitutes in order to avoid potentially fatal cardiac or systemic consequences. Although survival and quality of life is enhanced for many patients treated surgically, currently available valve substitutes remain imperfect.

Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves.

Background And Aim Of The Study: The roles of cardiac valvular interstitial cells (VIC) in extracellular matrix remodeling in fetal development, adaptation and response to injury are largely unknown.

Methods: The phenotype of VIC was studied in health (normal adult human and sheep), development (fetal human and sheep), disease (human mitral valves with myxomatous degeneration), adaptation (clinical pulmonary to aortic valve autografts) and tissue-engineered heart valves matured in vitro and remodeled in vivo. Cell phenotype was assessed using expression of vimentin (V), alpha-smooth muscle actin (SMA, A), matrix metalloproteinase (MMP)-13/collagenase-3 (M), and SMemb (S).

Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site.

Objective: We studied the pathologic features, cellular phenotypes, and matrix remodeling of clinical pulmonary-to-aortic valve transplants functioning up to 6 years.

Methods: Nine autografts and associated vascular walls early (2-10 weeks) and late (3-6 years) postoperatively were examined by using routine morphologic methods and immunohistochemistry. In 4 cases autograft and homograft cusps were obtained from the same patients.

Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques.

Background: We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques.

Methods And Results: To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE-/-) that express collagenase-resistant collagen-I (ColR/R/apoE-/-, n=12) or wild-type collagen-expressing mice (Col+/+/apoE-/-, n=12).

Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells.

Tissue engineering may offer patients new options when replacement or repair of an organ is needed. However, most tissues will require a microvascular network to supply oxygen and nutrients. One strategy for creating a microvascular network would be promotion of vasculogenesis in situ by seeding vascular progenitor cells within the biopolymeric construct.