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PubMed2005

Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression.

Large artery stiffening increases cardiovascular risk and promotes isolated systolic hypertension which is more prevalent in elderly women than men. Variation in sex steroid levels between males and females and throughout life may modulate arterial stiffness. We hypothesized that sex steroids directly influence expression of important structural proteins which determine arterial biomechanical properties. Human aortic smooth muscle cells were incubated with physiological concentrations of 17beta-estradiol, progesterone, 17beta-estradiol and progesterone, or testosterone for 4 weeks. Collagen, elastin, and fibrillin-1 deposition was examined (histochemistry/immunohistochemistry). Gene and protein expression of 2 important matrix metalloproteinases (MMPs), MMPs 2 and 3, regulating matrix turnover was assessed. All sex steroids reduced collagen deposition relative to control (100%). However, the reduction was greater with female sex steroids than testosterone (control, 100%; 17beta-estradiol plus progesterone, 20+/-2%; testosterone 74+/-12%, P<0.001). Female sex steroids increased elastin deposition compared with control (control, 100%; 17beta-estradiol, 540+/-60%; progesterone, 290+/-40%; 17beta-estradiol plus progesterone, 400+/-80%, all P<0.01). The elastin/collagen ratio was >11-fold higher in the presence of 17beta-estradiol and progesterone compared with testosterone. Fibrillin-1 deposition was doubled in the presence of female sex steroids (17beta-estradiol plus progesterone) compared with testosterone (P<0.01). MMP-2 gene and protein expression was unaffected by any sex steroid. Testosterone increased both gene and protein expression of MMP-3 relative to both control and female sex steroids (P<0.01). This may contribute to degradation of elastic matrix proteins. In conclusion, female sex steroids promote an elastic matrix profile, which likely contributes to variation in large artery stiffness observed between sexes and with changes in hormonal status across the lifespan.

Androgens↗
PubMed1996

Molecular methods of enhancing lumbar spine fusion.

OBJECTIVE: An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials. METHODS: Four similar canines received unilateral posterolateral fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and L6-L7. The experiments were grouped as follows: Group A, autogenous bone harvested from the iliac crest; Group B, autogenous bone and collagen; Group C, no implant; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level. RESULTS: For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls. CONCLUSION: The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.

Animals↗
PubMed2006

IL-1beta decreases the elastic modulus of human tenocytes.

Cellular responses to mechanical stimuli are regulated by interactions with the extracellular matrix, which, in turn, are strongly influenced by the degree of cell stiffness (Young's modulus). It was hypothesized that a more elastic cell could better withstand the rigors of remodeling and mechanical loading. It was further hypothesized that interleukin-1beta (IL-1beta) would modulate intracellular cytoskeleton polymerization and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1beta to alter the Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to the strain, E = stress/strain = (F/A)/(deltaL/L0), where L0 is the equilibrium length, deltaL is the length change under the applied stress, F is the force applied, and A is the area over which the force is applied. Human tenocytes were incubated with 100 pM recombinant human IL-1beta for 5 days. The Young's modulus was reduced by 27-63%. Actin filaments were disrupted in >75% of IL-1beta-treated cells, resulting in a stellate shape. In contrast, immunostaining of alpha-tubulin showed increased intensity in IL-1beta-treated tenocytes. Human tenocytes in IL-1beta-treated bioartificial tendons were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1beta reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or downregulating the expression of actin and upregulating the expression of tubulins. The reduction in cell modulus may help cells to survive excessive mechanical loading that may occur in damaged or healing tendons.

Actin Cytoskeleton↗
PubMed2003

Are the material properties and matrix composition of equine flexor and extensor tendons determined by their functions?

REASONS FOR PERFORMING STUDY: Injury to the superficial digital flexor tendon (SDFT) is common in competition horses. The SDFT contributes to locomotory efficiency by storing energy; such tendons have low safety margins. Tendons which merely position the limb, including the opposing common digital extensor tendon (CDET), are rarely injured. The current failure of strategies to prevent or effectively treat injury to the SDFT indicates the importance of understanding how it differs from tendons which are not injury-prone. HYPOTHESIS: That the structural and material properties and matrix composition of the SDFT and CDET differ, reflecting their specific functional requirements in vivo. METHODS: Forelimb tendons were harvested from 26 mature horses and loaded to failure prior to matrix composition analysis of specimens. RESULTS: The SDFT had a significantly higher cross-sectional area, structural stiffness, failure load and failure strain and a lower elastic modulus than the CDET (P < 0.0001). CONCLUSIONS: The SDFT has conflicting requirements for strength and elasticity; although as a whole it is a stiffer structure than the CDET, differences in the matrix molecular composition including water and total sulphated glycosaminoglycan contents allow it to remain more elastic as a material. POTENTIAL RELEVANCE: Further information on how the two tendons attain these different properties may be of use in the development of prevention and treatment strategies for SDFT rupture.

Animals↗
PubMed2000

Dynamic mechanical characterization of a mutable collagenous tissue: response of sea cucumber dermis to cell lysis and dermal extracts.

The dermis of the holothurian Cucumaria frondosa is a mutable collagenous tissue (MCT). In this study, the inner and outer regions of the dermis were separated and used to make two different tissue extracts. These extracts were applied to intact pieces of dermis, one invoking a stiff mechanical state and the other invoking a compliant state. The extracts were effective on tissues incubated in artificial sea water (ASW) and in those incubated in Ca(2+)-chelated ASW. Furthermore, the extracts were effective on both fresh tissues and tissues in which the cells had been lysed by freeze-thawing, indicating that the sites of action are in the extracellular matrix. Dynamic oscillatory shear tests and analyses were used to measure both the dynamic shear stiffness (G*) and the relative damping (tan delta ) of the tissue. These two parameters proved to be inversely related to each other (i.e. when G* increased, tan delta decreased). A theoretical viscoelastic model is constructed to interpret the results of these tests. It is concluded that changes in the mechanical state of the tissue involve interactions between elastic elements within the tissue rather than an alteration of its viscous components.

Animals↗
PubMed2005

Cardiac transgenic matrix metalloproteinase-2 expression directly induces impaired contractility.

OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) plays a major role in dysfunctional ventricular remodeling following myocardial injury induced by ischemia/reperfusion and heart failure. To directly assess the role of MMP-2 in the absence of superimposed injury, we generated cardiac-specific, constitutively active MMP-2 transgenic mice. METHODS: Morphologic and functional studies were carried out using both intact and demembranated (skinned) right ventricular trabeculae dissected from hearts of 8-month-old MMP-2 transgenic mice and wild-type controls (WT). RESULTS: Electron micrographs showed that compared to WT, MMP-2 myocardium had no gross, ultrastructural changes (no myocyte dropout or gross fibrosis). However, MMP-2 myocardium contained fibroblasts with abundant rough endoplasmic reticulum, consistent with an activated synthetic phenotype, suggesting extracellular matrix remodeling in MMP-2 trabeculae. Consistent with remodeling, mechanical studies found increased stiffness of intact unstimulated trabeculae (increasing sarcomere lengths from 2 to 2.3 microm caused a greater rise of passive muscle force for MMP-2 trabeculae versus WT). With electrical stimulation, MMP-2 trabeculae generated substantially less active force at all sarcomere lengths. Moreover, inotropic responses to increases of bath [Ca2+], pacing frequency, and isoproterenol were all significantly reduced versus WT trabeculae. Skinned fiber assessment of myofilament function revealed that maximum Ca2+-activated force of skinned MMP-2 trabeculae was reduced to approximately 50% of WT, suggesting a myofilament contraction defect. CONCLUSION: Cardiac-specific, constitutively active MMP-2 expression leads to impaired contraction and diminished responses to inotropic stimulation. These findings indicate that MMP-2 can directly impair ventricular function in the absence of superimposed injury.

Actin Cytoskeleton↗
PubMed2007

Optimization of UV cross-linking density for durable and nontoxic collagen GAG dermal substitute.

Artificial dermal constructs, based upon collagen-glycosaminoglycan matrices (CGMs), provide new options in treating skin defects. However, their clinical effectiveness may be limited by cytotoxicity related to residual aldehydes left over from the manufacturing process. Although both chemical and dehydrothermal (DHT) cross-linking are used to produce CGMs, we hypothesize that optimized nonchemical cross-linking, using ultra-violet (UV) and DHT treatment combinations, may limit cytotoxicity without sacrificing mechanical strength. Porous CGMs were physically cross-linked using a combination of DHT and varying intensities of UV light. These were compared to glutaraldehyde cross-linked controls. Human keratinocytes were seeded in each matrix, and cellular proliferation measured using a microculture tetrazolium dye assay. A scoring system (based on the in vitro contraction rate, stiffness, and cellular growth of a small cylindrical specimen) was developed to assess the best overall physical cross-linking method. More cellular growth was observed in the 90-120 min UV cross-linked group than in the glutaraldehyde-treated group (p < 0.05). Stiffness was maximized after 0-30 min of UV cross-linking. On the basis of our scoring system, DHT combined with 45 min of UV cross-linking produced the best overall matrix in terms of cellular growth and physical durability. UV cross-linked collagen-based biomaterials could be a viable alternative for use in biological applications to eliminate glutaraldehyde-associated cytotoxicity.

Cell Proliferation↗
PubMed2000

Mechanisms involved in airway obstruction: the role of smooth muscle.

Structural changes in the airway walls that are probably driven by mediators released as a consequence of chronic allergic inflammation are prominent features of asthma. However, it is not clear how each of the many changes that occur in the airway wall contribute to altered airway function in asthma. Collagen deposition in the subepithelial matrix, around and inside the smooth muscle, would be expected to oppose the effect of smooth-muscle contraction. Conversely, geometric factors would result in exaggerated airway narrowing for a given degree of smooth-muscle shortening; decreased airway wall stiffness and increased airway narrowing for a given amount of force generated by the smooth muscle. Degradation of the matrix may alter the coupling between muscle and lung recoil, allowing exaggerated smooth-muscle shortening. Increase in muscle mass associated with preservation of its contractile capacity could be the most important contributor to exaggerated airway narrowing.

Airway Obstruction↗
PubMed2005

Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis.

It has been speculated that heart valve interstitial cells (VICs) maintain valvular tissue homeostasis through regulated extracellular matrix (primarily collagen) biosynthesis. VICs appear to be phenotypically plastic, inasmuch as they transdifferentiate into myofibroblasts during valve development, disease, and remodeling. Under normal physiological conditions, transvalvular pressures (TVPs) on the right and left side of the heart are vastly different. Hence, we hypothesize that higher left-side TVPs impose larger local tissue stress on VICs, which increases their stiffness through cytoskeletal composition, and that this relation affects collagen biosynthesis. To evaluate this hypothesis, isolated ovine VICs from the four heart valves were subjected to micropipette aspiration to assess cellular stiffness, and cytoskeletal composition and collagen biosynthesis were quantified by using the surrogates smooth muscle alpha-actin (SMA) and heat shock protein 47 (HSP47), respectively. VICs from the aortic and mitral valves were significantly stiffer (P < 0.001) than those from the pulmonary and tricuspid valves. Left-side isolated VICs contained significantly more (P < 0.001) SMA and HSP47 than right-side VICs. Mean VIC stiffness correlated well (r = 0.973) with TVP; SMA and HSP47 also correlated well (r = 0.996) with one another. Assays were repeated for VICs in situ, and, as with in vitro results, left-side VIC protein levels were significantly greater (P < 0.05). These findings suggest that VICs respond to local tissue stress by altering cellular stiffness (through SMA content) and collagen biosynthesis. This functional VIC stress-dependent biosynthetic relation may be crucial in maintaining valvular tissue homeostasis and also prove useful in understanding valvular pathologies.

Animals↗
PubMed1992

Biocompatibility and mechanical properties of a totally absorbable composite material for orthopaedic fixation devices.

Bioabsorbable polymer/inorganic phosphate fiber composites are prone to rapid degradation due to water sensitivity of the interface between the degradable polymer and the degradable fiber. This article describes successful fabrication and laboratory evaluation of a candidate bioabsorbable composite implant material with mechanical properties similar to bone. The composite studied was poly(ortho ester) reinforced with randomly-oriented, crystalline microfibers of calcium-sodium-metaphosphate. The component materials showed no acute cytotoxicity as determined by tissue culture agar overlay. Treating the microfibers with a diamine-silane coupling agent improved mechanical properties and slowed degradation in saline, but strength still decreased 50% in 1 week. When the composite material was then coated with a layer of matrix polymer alone it retained 70% of its strength and 70% of its stiffness after 4 weeks exposure to 7.4 pH Tris-buffered saline at body temperature. The marked improvement with the coating can be attributed to the hydrophobicity of poly(ortho esters).

Biodegradation, Environmental↗
PubMed2002

Lactic acid based PEU/HA and PEU/BCP composites: Dynamic mechanical characterization of hydrolysis.

Lactic acid based poly(ester-urethane) (PEU-BDI) and its composites with 20 and 40 vol.% bioceramic filler were characterized prior to their use as biocompatible and bioabsorbable artificial bone materials. Morphological, dynamic mechanical properties, and degradation of these either hydroxyapatite or biphasic calcium phosphate containing composites were determined. Addition of particulate bioactive filler increased the composite stiffness and the glass transition temperature, indicating strong interactions between the filler and matrix. Materials were sterilized by gamma-irradiation, which reduced the average molecular weights by 30-40%. However, dynamic mechanical properties were not significantly affected by irradiation. Specimens were immersed in 0.85 w/v saline at 37 degrees C for 5 weeks, and changes in molecular weights, mass, water absorption, and dynamic mechanical properties were recorded. All the composite materials showed promising dynamic mechanical performance over the 5 weeks of hydrolysis. Average molecular weights of PEU-BDI and its composites did not change substantially during the test period. PEU-BDI retained its modulus values relatively well, and although the moduli of the composite materials were much higher, especially at high filler content, they exhibited faster loss of mechanical integrity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Effect of short-term water storage on the elastic properties of some dental restorative materials--A resonant ultrasound spectroscopy study.

OBJECTIVES: This study was aimed to determine if short-term water storage would change elastic properties of dental composite materials. METHODS: Particulate filler composite resin and continuous unidirectional E-glass FRC materials were photopolymerized and additionally post-polymerized by heat for testing elastic properties with the Resonance Ultrasound Spectroscopy method as a function of time in water storage. The test specimens were stored in 37 degrees C water for up to 30 days. RESULTS: About 1% weight increase due to water sorption was observed in both materials with both polymerization methods. Water sorption did not change the resonance frequencies towards lower values, indicating no significant decrease in elastic properties in these materials. Because of high damping of the polymer composite materials leading to wide resonance peaks and low number of the recorded peaks, accurate determination of the elastic properties was not possible. SIGNIFICANCE: Results suggest that the most likely explanation for the previously observed decrease in bending stiffness of FRC materials is the decreased yield limit of the hydrated polymer matrix. It is important to recognize that water sorption has the effect on mechanical properties of dental composite materials by changing the yield limit of the matrix rather than by changing the elastic properties of the material.

Absorption↗
PubMed2004

Sensitivity of indentation testing to step-off edges and interface integrity in cartilage repair.

Step-off edges and tissue interfaces are prevalent in cartilage injury such as after intra-articular fracture and reduction, and in focal defects and surgical repair procedures such as osteochondral graft implantation. It would be useful to assess the function of injured or donor tissues near such step-off edges and the extent of integration at material interfaces. The objective of this study was to determine if indentation testing is sensitive to the presence of step-off edges and the integrity of material interfaces, in both in vitro simulated repair samples of bovine cartilage defect filled with fibrin matrix, and in vivo biological repair samples from a goat animal model. Indentation stiffness decreased at locations approaching a step-off edge, a lacerated interface, or an integrated interface in which the distal tissue was relatively soft. The indentation stiffness increased or remained constant when the site of indentation approached an integrated interface in which the distal tissue was relatively stiff or similar in stiffness to the tissue being tested. These results indicate that indentation testing is sensitive to step-off edges and interface integrity, and may be useful for assessing cartilage injury and for following the progression of tissue integration after surgical treatments.

Animals↗
PubMed1988

Nonlinear gross response analysis of a lumbar motion segment in combined sagittal loadings.

A 3-D nonlinear mathematical model is used to analyze the mechanical response of a lumbar L2-3 motion segment including the posterior elements when subjected to combined sagittal plane loads. The loadings consist of axial compression force, anterior and posterior shear forces, and flexion and extension moments. The facet articulation is modelled as a general moving contact problem and the ligaments as a collection of uniaxial elements. The disk nucleus is considered as an inviscid fluid and the annulus as a composite of collagenous fibers embedded in a matrix of ground substance. The presence of axial compression force reduces the segmental stiffness in flexion whereas a reverse trend is predicted in extension. In the presence of axial compression with and without sagittal shear force, flexion considerably increases the intradiscal pressure while extension reduces it. In other words, under an identical compression force, disk pressure is predicted to be noticeably larger in flexion than in extension. The segmental mechanical response in extension loadings is markedly influenced by the changes in the relative geometry of the articular surfaces at the lower regions. Finally, the deformation of the bony structures plays a significant role in the segmental mechanics under relatively large loads.

Biomechanical Phenomena↗
PubMed2001

The biomechanical effects of fatigue on the porcine bioprosthetic heart valve.

Characterization of the mechanisms of degeneration of porcine bioprosthetic heart valves (BHV) during long-term cyclic loading is required for predicting and ultimately preventing their failure. Isolation of purely mechanical effects from host biological ones is a necessary first step in understanding the fatigue process as a whole. Thus, in this review we focus on mechanical factors alone as a means of isolating their role in altering biomechanical properties and ultimately their contribution to the fatigue damage process. Mechanical evaluations included tension controlled biaxial, 3-point flexural, and uniaxial failure tests performed on cuspal tissue following 0, 50, 100, 200, and 300 x 10(6) in vitro accelerated test cycles. Overall, biaxial mechanical results indicate a decreasing radial extensibility that can be explained by stiffening of the effective collagen fiber network as well as a small decrease in the splay of the collagen fibers. Moreover, these results suggest that the loss in flexural rigidity with fatigue that we have previously measured (ASAIO 1999; 45:59-63) may not be because of loss of collagen stiffness alone, but also to fiber debonding and degradation of the amorphous extracellular matrix. We discuss the implications of these results that point toward the development of chemical-treatment methods that seek to maintain the integrity of the amorphous extracellular matrix to ultimately extend BHV long-term durability.

Animals↗
PubMed1995

Aging and matrix microdamage accumulation in human compact bone.

Bone matrix microdamage in bone matrix, evidenced as microcracks, occurs consequent to cyclic loading. Microdamage caused by in vivo loading has been described in human rib cortex; however, the existence and extent of microcracks in human long bone cortices are largely unknown. Using histomorphometric methods to examine the incidence and localization of microcracks in human femoral compact bone specimens, we found that the amount of microdamage present in femoral compact bone increases dramatically with increasing age. Least squares regression analysis showed that in males, microcrack density (Cr.De., #/mm2) increases exponentially with age (r2 = 0.70). In females, Cr.De. also increases as an exponential function of increasing age (r2 = 0.79), at a significantly higher rate than in male specimens (p < 0.001). The current studies indicate that with increasing age, bone microdamage accumulates more rapidly than intrinsic processes can effect its repair. A combination of cumulative loading history, focal changes in material properties and alteration in the ability of the tissue to perceive and/or react to microcracks may all play role in this accumulation of bone microdamage with aging. This accumulation of microdamage in bone will contribute to decreased strength and stiffness. In addition, and perhaps most significantly for understanding aging and increased bone fragility, matrix microdamage in composite materials like bone will result in a profoundly reduced resistance to fracture. The importance of this accumulation of matrix microdamage in human bone with increasing age in contributing to the increased fragility of the aging skeleton is discussed.

Adolescent↗
PubMed2001

Large artery stiffness: structural and genetic aspects.

1. Large artery stiffness is a principal determinant of pulse pressure and both are related to cardiovascular mortality independently of other major risk factors. A clearer understanding of the structural and genetic processes that contribute to large artery properties may provide novel approaches to therapy. 2. Age, atherosclerosis and gender are three important factors that contribute to large artery stiffening. Each influences the artery elastic matrix and its relationship to medial smooth muscle cells. Genetic and hormonal modulation of the extracellular matrix proteins and their regulators, including matrix metalloproteinases (MMPs), may account for some interindividual differences. 3. In a study of 213 healthy individuals and 105 patients with coronary artery disease (CAD), we examined whether stromelysin-1 (MMP-3) genotype, determined by the 5A/6A promoter polymorphism, influences large artery stiffening. In healthy individuals, the 5A/5A genotype was linked with stiffer large arteries and higher systolic blood pressure compared with other genotypes. 4. Genetic variation in the extracellular matrix protein fibrillin-1, using a pentanucleotide repeat polymorphism, was assessed as a potential determinant of large artery stiffness in patients with CAD. The 2-3 genotype was associated with stiffer large arteries, higher pulse pressure and more severe CAD than other genotypes. 5. Females experience a greater increase in large artery stiffness with age than males, with a time-course suggestive of sex steroid modulation. The mechanisms mediating such gender differences have not been established, but the known regulatory role of sex steroids with respect to MMPs likely contributes. 6. The demonstration that genetic and hormonal modulation of extracellular matrix components and MMPs contributes to age, atherosclerotic and gender-related differences in large artery mechanical properties suggests these proteins may be important targets for therapy.

Age Factors↗
PubMed2003

Effects of ACE inhibition versus non-ACE inhibitor antihypertensive treatment on myocardial fibrosis in patients with arterial hypertension. Retrospective analysis of 120 patients with left ventricular endomyocardial biopsies.

BACKGROUND AND PURPOSE: In experimental arterial hypertension, left ventricular hypertrophy (LVH) becomes pathologic with impaired myocardial function if myocardial fibrosis occurs. Myocardial fibrosis is associated with activated circulating or local renin-angiotensin-aldosterone systems. The primary objective of this retrospective study was to determine whether patients with arterial hypertension treated with angiotensin-converting enzyme inhibitors (ACEI) have less myocardial fibrosis than patients on non-ACEI treatment. MATERIAL AND METHODS: We examined left ventricular (LV) endomyocardial biopsies of 97 consecutive patients with hypertensive heart disease due to primary hypertension treated with either any ACEI for at least 6 months (n = 34; HTN + ACEI) or non-ACEI antihypertensive drugs (n = 63; HTN). Normal hearts designated for heart transplantation served as controls (n = 23; CTR). Myocyte diameter (MyoD) and collagen volume fraction (CVF) were measured by morphometry, and pro-matrix metalloproteinases (proMMPs) 2 and 9 by zymography. In a subset of 35 patients, LV myocardial stiffness was determined by left heart catheterization with calculation of stiffness constant k. RESULTS: In HTN + ACEI or HTN, MyoD (21.8 +/- 0.3 micro m and 22.4 +/- 0.3 micro m, respectively) and CVF (5.3 +/- 0.6% and 7.6 +/- 0.7%, respectively) were increased (p < 0.01) compared with CTR (16.0 +/- 0.4 micro m and 0.5 +/- 0.2%, respectively). In HTN + ACEI, CVF was significantly lower (p < 0.02) and proMMP 2 was higher (0.063 +/- 0.013 OD/mg) compared with HTN (0.037 +/- 0.006 OD/mg; p < 0.05) while no significant difference of MyoD was evident. We found no correlation between CVF and MyoD (r = 0.13; p = 0.47), a positive correlation between k and CVF (r = 0.71; p < 0.00001), and no correlation between k and MyoD (r = 0.22; p = 0.24). CONCLUSION: In patients with hypertensive heart disease, myocyte hypertrophy and myocardial fibrosis are present. Myocardial fibrosis and not myocyte hypertrophy determines myocardial stiffness. ACEI appear to diminish myocardial fibrosis associated with enhanced collagen degradation irrespective of LVH regression.

Aged↗