elastin and Aortic-Valve-Insufficiency

After pulmonary autograft replacement of the aortic valve and root, the pulmonary artery (PA) wall is subjected to higher pressures. Concern exists that this may lead to structural and functional changes in the implanted autograft and subsequent aortic root dilatation and neoaortic regurgitation. We therefore assessed root dimensions and neoaortic regurgitation, morphological structure, and mechanical behavior in patients who underwent the Ross operation.. Seventy-four patients who were randomized to undergo aortic valve replacement with an aortic homograft or a pulmonary autograft were followed up echocardiographically for up to 4 years and had their aortic root dimensions measured at the level of the annulus, sinuses, and sinotubular junction. In a separate series of 18 patients who underwent pulmonary autograft surgery and 8 normal organ donors, samples from the PA and aorta were analyzed for medial wall thickness, distribution of the staining of collagen and elastin, and elastin fragmentation. Finally, stress-strain curves were obtained from samples of the PA and aorta from 9 patients who underwent pulmonary autograft surgery and from 1 patient in whom a 4-month-old autograft was explanted. No patient in either group had aortic dilatation at any level of >20% or more than mild aortic regurgitation at up to 4 years of follow-up. The aortic media was thicker in both autografts and normal donors (P:<0.01), and there was a trend for the PA media to be thicker in the autograft group. Elastic fiber in all aortas showed little or no variation, whereas in the PA, there was considerable variation in fragmentation. Patients with higher preoperative PA pressures tended to have lower fragmentation scores (chi(2) P:<0.01). The lower stiffness modulus, higher stiffness modulus, and maximum tensile strength of the aorta was 34% to 38% higher than that of the PA (P:<0.01); however, the 4-month-old autograft appeared to show adaptation in mechanical behavior.. In our series of patients, there was no significant progressive dilatation of the aortic root. We demonstrated differences in the anatomic structure and mechanical behavior of the PA in vitro and highlighted histological and mechanical modes of adaptation.

Topics: Adolescent; Adult; Aged; Aorta; Aortic Valve; Aortic Valve Insufficiency; Cardiac Surgical Procedures; Child; Collagen; Echocardiography; Elastin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pulmonary Artery; Reproducibility of Results; Stress, Mechanical; Transplantation, Autologous; Transplantation, Homologous; Tunica Media

Clinical studies have revealed a greater risk of pulmonary autograft dilation after the Ross procedure in patients with preoperative aortic insufficiency (AI). The present study examined whether the morphologic, biomechanical, and cellular properties of the pulmonary artery (PA) from patients with AI were phenotypically different compared with patients diagnosed with aortic stenosis (AS).. PA segments were harvested from patients undergoing the Ross procedure for AS (n = 16) and AI (n = 6). Preoperative aortic annulus was significantly larger (P < 0.05) in patients with AI (28.5 ± 1.8 mm) vs AS (22.8 ± 1.2 mm). Morphologic, biomechanical, and cellular phenotypes of the PA were analyzed.. Collagen and elastin content in the media of the PA wall were similar in patients with AS and AI. Elastic modulus and energy loss of the PA were not significantly different between the groups. In the media of the PA, expression of a panel of vascular smooth muscle cell-specific proteins were similar in patients with AS and AI. In contrast, nonmuscle myosin IIB protein levels in the PA of AS patients were significantly higher compared with AI patients, and immunofluorescence identified staining in α-smooth muscle actin-positive vascular smooth muscle cells.. Despite similar morphological and biomechanical properties, the disparate expression of nonmuscle myosin IIB protein distinguishes the PA of patients with AI from patients with AS. The biological role in vascular smooth muscle cells and the potential contribution of nonmuscle myosin IIB to pulmonary autograft dilation in a subset of AI patients after the Ross procedure remain to be determined.

Topics: Actins; Aorta; Aortic Valve Insufficiency; Aortic Valve Stenosis; Autografts; Biomechanical Phenomena; Collagen; Echocardiography, Doppler; Elastic Modulus; Elastin; Female; Humans; Male; Middle Aged; Myocytes, Smooth Muscle; Nonmuscle Myosin Type IIB; Pulmonary Artery; Pulmonary Valve; Tunica Media

AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR. Graphic Abstract: A graphic abstract is available for this article.

Topics: Adult; Aged; Aorta; Aortic Valve Insufficiency; Aortic Valve Stenosis; Apoptosis; Case-Control Studies; Collagen; Dilatation, Pathologic; Elastin; Endothelial Cells; Female; Fibrillins; Humans; Immunohistochemistry; Male; Middle Aged; Nitric Oxide Synthase Type III; Vascular Remodeling; Young Adult

Bicuspid aortic valve (BAV) is associated with aortic wall alterations. We aimed to detect any correlation between aortic elasticity and genetic and biomolecular patterns of elastin.. Forty-nine BAV patients (mean age: 38 ± 17.05) were prospectively enrolled. A blood sample was drawn for analysis of a single nucleotide polymorphism of elastin gene (ELN rs2071307) responsible for misfolding of elastin, and for the amount of elastin soluble fragments (ESF) in the plasma. Aortic dimensions and elastic properties were determined by echocardiography, aortic stiffness (AS) by M-mode analysis, and longitudinal strain (LS) of the ascending aorta (AA) by speckle-tracking echocardiography; values of aortic strain were compared with 45 age-matched subjects (mean age: 33 ± 9.67) with tricuspid aortic valve (TAV). BAV patients had greater aortic dimensions [Valsalva sinus (P = 0.004), sinotubular junction (P = 0.013), AA (P < 0.001)] and stiffness (P = 0.002) but lower LS (P = 0.04) than those with TAV. Results from comparisons of mutated genotype patients (AA, n = 10) with heterozygous (GA, n = 21) and wild-types ones (GG, n = 16) revealed that the presence of mutation was associated with increased ESF (P = 0.010 GG vs. GA; P = 0.035 GA vs. AA), larger AA (P = 0.019 GG vs. GA; P = 0.001 GG vs. AA), and lower LS (P = 0.032 GG vs. AA). Patients with a dilated AA showed greater ESF (P < 0.001), greater AS (P = 0.007), and lower LS of the AA (P = 0.002) than those with a normal AA. The same parameters were not significantly different comparing patients with moderate or severe aortic valve disease and patients with less than moderate valve disease.. Our results show a close correlation between genetic and biomolecular patterns of elastin and mechanical properties of the aorta in patients with BAV.

Topics: Adult; Aortic Valve; Aortic Valve Insufficiency; Bicuspid Aortic Valve Disease; Case-Control Studies; Echocardiography; Elastin; Female; Gene Expression Regulation; Genotype; Heart Defects, Congenital; Heart Valve Diseases; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Prospective Studies; Reference Values; Young Adult

Degenerative heart valve disease is a life-threatening disease affecting about 3% of the population over 65 years. Up to date, cardiac surgery with heart valve replacement is the only available therapy. The disease is characterized by degenerative disorganization of the heart valve structure and alterations in the residing cell populations. Causes and mechanisms of disease genesis are still not fully understood and until now pharmacological therapies are not available. Thus there is enormous interest in new technologies that enable a better characterization of structure and composition of diseased valves. Currently most research techniques demand for extensive processing of extracted valve material. We present a novel approach combining coherent anti-Stokes Raman scattering, endogenous two-photon excited fluorescence and second harmonic generation. Cusp constituents can be examined simultaneously, three-dimensionally and without extensive manipulation of the sample enabling impressive insights into a complex disease.

Topics: Adipocytes; Aged; Aged, 80 and over; Aorta; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Collagen; Compressive Strength; DNA; Elastin; Humans; Image Processing, Computer-Assisted; Lithostathine; Male; Microscopy, Fluorescence; Optics and Photonics; Photons; Spectrum Analysis, Raman

Significant dilation of the pulmonary autograft after the Ross operation is problematic and requires reoperation. Autograft remodeling occurs in response to the immediate rise in pressure and consequent wall stress. The stress-strain response of the pulmonary root plays an important role in understanding the structural and functional changes of the autograft following the Ross procedure. At present, limited data are available on the mechanical properties of fresh human pulmonary roots; hence, the study aim was to determine the regional mechanical properties of human pulmonary roots.. Eighteen fresh healthy specimens of human pulmonary root were obtained from the California Transplant Donor Network (Oakland, CA, USA). Five regions of the pulmonary root--anterior and posterior pulmonary artery (PA), and each of the three sinuses--were subjected to displacement-controlled equibiaxial stretch testing within 24 h of cross-clamp time. Comparisons between the different regions of the pulmonary root were made based on tissue stiffness at physiologic stress. Histologic analyses were also performed of the fibrous structures of the PA and sinuses.. Human PA and sinuses demonstrated a nonlinear response to loading, with no directional dependency to biaxial loading. The anterior PA was significantly more compliant than the posterior PA and the three sinuses in both circumferential and longitudinal directions (p < 0.04). However, there was no significant difference between the stiffness of the posterior PA and that of the three sinuses (p > 0.43), or among the three sinuses (p > 0.30) in the two directions. A tight, more dense weave of elastin was found in the anterior PA than in either the posterior PA or the sinuses.. Significant inherent differences in compliance were demonstrated among different regions of the human pulmonary root. These regional differences may impact upon pulmonary autograft remodeling following the Ross operation, and also influence late autograft dilation.

Topics: Adult; Aortic Valve; Aortic Valve Insufficiency; Biomechanical Phenomena; Collagen; Compliance; Elastin; Humans; In Vitro Techniques; Middle Aged; Models, Cardiovascular; Pulmonary Artery; Stress, Mechanical; Transplantation, Autologous

Lysyl oxidases (Lox), which are members of the amine oxidase family, are involved in the maturation of elastic lamellae and collagen fibers. Modifications of amine oxidases in idiopathic annulo-aortic ectasia disease (IAAED) have never been investigated. Our aim was to examine the expression of several proteins that might interfere with elastic fiber organization in control (n=10) and IAAED (n=18) aortic tissues obtained at surgery. Expression of amine oxidases and semicarbazide-sensitive amine oxidase (SSAO), and cellular phenotypic markers were examined by immunohistopathology and confocal microscopy. The expression of these proteins was assessed in relation to clinical and histomorphological features of the arterial wall. In control aorta, SSAO staining was expressed along elastic lamellae, whereas in aneurysmal areas of IAAED, SSAO was markedly decreased, in association with severe disorganization of elastic lamellae. Smooth muscle myosin heavy chain was also decreased in IAAED compared with controls, indicating smooth muscle cell dedifferentiation. Multiple regression analysis showed that elastic lamellar thickness (ELT) was correlated positively with the SSAO:elastin ratio and negatively with the Lox:elastin ratio, and that the clinical features of IAAED (aneurysm, thoracic aorta diameter, and aortic insufficiency) were positively correlated with ELT but not with SSAO. The relationship between SSAO expression and ELT suggests that this amine oxidase may be involved in elastic fiber organization. However, in advanced IAAED, the deficit in SSAO expression could be secondary to the decrease and fragmentation of elastic fibers and/or to vascular smooth muscle cell dedifferentiation.

Topics: Amine Oxidase (Copper-Containing); Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Valve Insufficiency; Cell Differentiation; Elastin; Extracellular Matrix; Female; Humans; Immunohistochemistry; Male; Microscopy, Confocal; Middle Aged; Muscle, Smooth, Vascular; Myosin Heavy Chains; Protein-Lysine 6-Oxidase; Regression Analysis

To quantitate the pathologic features of carcinoid plaques in a relatively large number of surgical specimens from a single institution.. Medical records, operative reports, and surgical specimens were reviewed from all patients with carcinoid heart disease who underwent cardiac valvular surgery at Mayo Clinic, Rochester, Minn, between 1980 and 2000.. The study group included 75 patients (45 men, 30 women) who ranged in age from 26 to 78 years (mean, 59 years). From these 75 patients, 139 valves had been excised surgically (73 tricuspid, 55 pulmonary, 6 mitral, 5 aortic). Pure regurgitation was the most common dysfunctional state of the tricuspid valve (80% [60/75]), mitral valve (97% [32/33]), and aortic valve (96% [23/24]). The pulmonary valve was more often both stenotic and insufficient (52% [37/71]) than purely regurgitant (30% [21/71]). In all cases, valve dysfunction was attributed to the presence of carcinoid plaques, which caused both thickening and retraction. Thickening was the result of both cellular proliferation and deposition of extracellular matrix. Proliferation of myofibroblasts was observed in all plaques and was mild in 49% (68/139) and moderate or severe in 51% (71/139). Extracellular matrix included collagen (in 99% of the 139 valves), myxoid ground substance (98% [136/139]), and elastin (20% [28/139]). Carcinoid plaques were also involved by neovascularization (94% [131/139]), chronic inflammation (94% [131/139]), and mast cell infiltration (64% [89/139]). Severe thickening was attributable primarily to collagen deposition in tricuspid valves and to myofibroblast proliferation and myxoid matrix in pulmonary valves.. Among patients undergoing valvular surgery for carcinoid heart disease, tricuspid and pulmonary valves represented 92% of the excised valves (128/ 139). Although numerous cellular and extracellular features were common to the carcinoid plaques, variability in their relative expression produced appreciable differences in the histologic appearance among the plaques.

Topics: Adult; Aged; Aortic Valve Insufficiency; Carcinoid Heart Disease; Collagen; Elastin; Female; Fibroblasts; Hemodynamics; Humans; Hyperplasia; Inflammation; Male; Mast Cells; Middle Aged; Mitral Valve Insufficiency; Neovascularization, Pathologic; Pulmonary Valve Insufficiency; Retrospective Studies; Severity of Illness Index; Tricuspid Valve Insufficiency

Since structure-function correlations have not been determined for cryopreserved allograft heart valves, we studied 20 explanted valves in place several hours to nine years, as either orthotopic aortic valves/root replacements or right ventricle to pulmonary artery conduits. They were explanted primarily due to growth-related conduit or valve stenosis, valve regurgitation, or infection. Controls included seven unused cryopreserved allograft valves and 16 aortic valves removed from transplanted allograft hearts obtained at either autopsy (n = 15) or retransplantation (n = 1), two days to four years postoperatively, following myocardial rejection (n = 4), graft coronary arteriosclerosis (n = 4), and other (n = 8). Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies (to allow identification/localization of endothelial cells, mononuclear inflammatory cells, and T and B lymphocyte subsets). Cryopreserved allograft valves implanted more than one day had progressively severe loss of normal structure and were devoid of surface endothelium and stainable deep connective tissue cells. Inflammatory cellularity varied from none (most valves) to prominent (primarily T lymphocytes in one valve). Transmission electron microscopy of three long term valvular allografts revealed no viable cells, remarkable preservation of the collagenous valve matrix and focal cell-oriented calcification. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including layered architecture, endothelium and deep connective tissue cells; inflammatory infiltrates were generally sparse, even in cases with fatal myocardial rejection. We conclude that cryopreserved allograft valves are morphologically non-viable valves, whose structural basis for function seems primarily related to the largely preserved collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; B-Lymphocyte Subsets; Calcinosis; Cell Survival; Collagen; Connective Tissue; Coronary Artery Disease; Cryopreservation; Elastin; Endocarditis, Bacterial; Endothelium; Follow-Up Studies; Graft Rejection; Humans; Immunohistochemistry; Leukocytes, Mononuclear; Microscopy, Electron; Pulmonary Valve; Pulmonary Valve Insufficiency; Pulmonary Valve Stenosis; Radiography; T-Lymphocyte Subsets; Tissue Preservation; Transplantation, Homologous

Topics: Adrenergic beta-Antagonists; Aortic Aneurysm; Aortic Dissection; Aortic Valve Insufficiency; Elastin; Fibrillins; Genetic Counseling; Humans; Marfan Syndrome; Microfilament Proteins; Mitral Valve Insufficiency; Myofibrils; Patient Care Team; Phenotype

Topics: Animals; Aortic Valve; Aortic Valve Insufficiency; Cartilage; Cattle; Collagen; Connective Tissue; Elastin; Formaldehyde; Humans; Lymphocytes; Necrosis; Rupture, Spontaneous; Swine; Transplantation, Heterologous

Topics: Adult; Amino Acids; Aorta, Thoracic; Aortic Valve; Aortic Valve Insufficiency; Collagen; Deafness; Elastin; Humans; Lipids; Male; Mitral Valve Insufficiency; Myocardium; Nose Deformities, Acquired; Phospholipids; Polychondritis, Relapsing