Proteinases and restenosis in the human coronary artery: extracellular matrix production exceeds the expression of proteolytic activity

Tyagi, Suresh C.; Meyer, Louis J.; Schmaltz, Richard A.; Reddy, Hanumanth K.; Voelker, Donald J.

doi:10.1016/0021-9150(95)05520-7

Cited by 74 publications

(37 citation statements)

References 37 publications

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“…The withdrawal of Hcy reduces the Hcy-mediated increase in HR (Figure 3). These results suggest that Hcy decreases elastin/collagen and increases HR (Tyagi et al, 1995;Sood et al, 2002). However, the inverse relationship shown for the elastin/collagen ratio ( Figure 3B) and heart rate ( Figure 3A) for mice, rats, rabbits and humans may be entirely unrelated.…”

Section: Hcy Increases Heart Ratementioning

confidence: 45%

Arrhythmia and neuronal/endothelial myocyte uncoupling in hyperhomocysteinemia

Rosenberger

Moshal

Kartha

et al. 2006

Archives of Physiology and Biochemistry

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Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with arrhythmogenesis and sudden cardiac death (SCD). Hcy decreases constitutive neuronal and endothelial nitric oxide (NO), and cardiac diastolic relaxation. Hcy increases the iNOS/NO, peroxynitrite, mitochondrial NADPH oxidase, and suppresses superoxide dismutase (SOD) and redoxins. Hcy activates matrix metalloproteinase (MMP), disrupts connexin-43 and increases collagen/elastin ratio. The disruption of connexin-43 and accumulation of collagen (fibrosis) disrupt the normal pattern of cardiac conduction and attenuate NO transport from endothelium to myocyte (E-M) causing E-M uncoupling, leading to a pro-arrhythmic environment. The goal of this review is to elaborate the mechanism of Hcy-mediated iNOS/NO in E-M uncoupling and SCD. It is known that Hcy creates arrhythmogenic substrates (i.e. increase in collagen/elastin ratio and disruption in connexin-43) and exacerbates heart failure during chronic volume overload. Also, Hcy behaves as an agonist to N-methyl-D-aspartate (NMDA, an excitatory neurotransmitter) receptor-1, and blockade of NMDA-R1 reduces the increase in heart rate-evoked by NMDAanalog and reduces SCD. This review suggest that Hcy increases iNOS/NO, superoxide, metalloproteinase activity, and disrupts connexin-43, exacerbates endothelial-myocyte uncoupling and cardiac failure secondary to inducing NMDA-R1.

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Section: Hcy Increases Heart Ratementioning

confidence: 45%

Arrhythmia and neuronal/endothelial myocyte uncoupling in hyperhomocysteinemia

Rosenberger

Moshal

Kartha

et al. 2006

Archives of Physiology and Biochemistry

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“…A reduced enzyme activity leads to the accumulation of extracellular matrix and the progression of atherosclerosis. 6 Accordingly, Tyagi et al 38 have reported that weight for weight, atherosclerotic vessels contain more collagen and less MMP activity than do normal arteries. On the other hand, focal overexpression of matrix-degrading activity in crucial plaque sites can trigger the rupture of the fibrous cap and acute thrombotic events.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects

Gnasso

Motti

Irace

et al. 2000

ATVB

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Abstract-A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63Ϯ0.09, 0.55Ϯ0.06, and 0.53Ϯ0.04 cm [meanϮSD], PϽ0.005 by ANOVA; intima-media thickness was 765Ϯ116, 670Ϯ116, and 630Ϯ92 m [meanϮSD], PϽ0.05 by ANOVA). Wall shear stress, calculated as blood velocityϫblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4Ϯ2.9, 13.5Ϯ3.5, and 12.6Ϯ1.9 dyne/cm 2 [meanϮSD], PϽ0.05 by ANOVA).The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.

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“…The samples were applied without reduction to a 7.5% polyacrylamide slab gel impregnated with 1 mg/mL gelatin (15). After electrophoresis, the gel was washed at room temperature for 30 min in a washing buffer (50 mmol/L Tris chloride, pH 7.5, 15 mmol/L calcium chloride, 1 mol/L zinc chloride, and 2.5% Triton X-100 [Nichitionogene Tenside, Marke von Union Carbide, USA]); it was then incubated overnight at 37°C and shaken in the same buffer, but containing 1% rather than 2.5% Triton X-100.…”

Section: Analysis Of Gelatinase Productionmentioning

confidence: 99%