The Etiological Heterogeneity of Bicuspid Aortopathy between Ascending and Root Morphotype.

BACKGROUND: Valve-related hemodynamics and intrinsically regulated matrix proteases are 2 determined pathogenetic factors associated with medial elastin degeneration in bicuspid aortopathy. This study analyzed the association between elastic fiber deterioration and the 2 pathogenetic factors in ascending and root morphotypes, aiming to elucidate the etiological heterogeneity between the 2 morphotypes. METHODS: Four-dimensional flow cardiac magnetic resonance was used to measure the regional wall shear stress (WSS) on the ascending aorta, and matrix metalloproteinase (MMP) expression was assessed by immunoblotting. After histopathology analysis of aortic tissue, we assessed whether elevated regional WSS and increased MMP expression corresponded with medial elastin thinning. RESULTS: Increased regional WSS corresponded with medial elastin thinning in both morphotypes. Increased expression of different MMP isoforms corresponded with medial elastin degeneration in bicuspid aortopathy. The significantly increased expression of MMP-2 corresponded with a decrease of elastic fiber thickness in the ascending morphotype (P = .046), whereas elastic fiber thinning was associated with high levels of MMP-3 expression (P = .012) in the root morphotype. No association was observed between regional WSS and MMP expression. CONCLUSION: There is no difference in the effect of valve-related hemodynamics between ascending and root morphotype, and MMPs are not involved in the process of elastic fiber degeneration induced by increased WSS. The increased expression of different MMP isoforms was observed in the context of elastic fiber degeneration between the 2 morphotypes, implying that heterogeneity between them is revealed in the different intrinsic pathway of medial elastin degradation.

Plasma Phospholipid Transfer Protein Promotes Platelet Aggregation.

It remains unclear whether plasma phospholipid transfer protein (PLTP) is involved in hyper-coagulation or hypo-coagulation. This study investigated the direct effect of PLTP on platelet aggregation and the underlying mechanism. Washed platelets from humans or mice and mouse platelet-rich plasma and human recombinant PLTP were isolated. PLTP is present in human platelets. We assessed adenosine diphosphate (ADP)-, collagen- and thrombin-induced platelet aggregation, phosphatidylserine externalization and photothrombosis-induced cerebral infarction in mice. PLTP over-expression increased platelet aggregation, while PLTP deficiency had the opposing reaction. Human recombinant PLTP increased both mouse and human platelet aggregation in a dose-dependent manner. Phosphatidylserine externalization provides a water/lipid surface for the interaction of coagulation factors, which accelerates thrombosis. Compared with wild-type controls, platelets from PLTP transgenic mice had significantly more phosphatidylserine on the exterior surface of the plasma membrane, whereas platelets from PLTP-deficient mice had significantly less phosphatidylserine on the surface, thus PLTP influences fibrinogen binding on the plasma membrane. Moreover, recombinant PLTP together with ADP significantly increased phosphatidylserine exposure on the plasma membrane of PLTP-deficient platelets, thereby increasing fibrinogen binding. PLTP over-expression significantly accelerated the incidence of photothrombosis-induced infarction in mice, whereas PLTP deficiency significantly reduced the frequency of infarction. We concluded that PLTP promotes phosphatidylserine externalization at the plasma membrane of platelets and accelerates ADP- or collagen-induced platelet aggregation. This effect plays an important role in the initiation of thrombin generation and platelet aggregation under sheer stress conditions. Thus, PLTP is involved in hyper-coagulation. Therefore, PLTP inhibition could be a novel approach for countering thrombosis.

Efficiency of trapping methylglyoxal by phenols and phenolic acids.

The carbonyl stress that leads to the formation of advanced glycation end products (AGEs) has drawn much attention recently because of its micro- and macrovascular implications. During monitoring of methylglyoxal (MG), the efficiency of phenolics to directly trap MG can be demonstrated. Twenty compounds consisting of a single benzene ring structure with the addition of at least one hydroxyl group were allowed to react with MG at 37 °C for 1 h under physiological conditions in pH 7.4 phosphate buffer solution. Compounds composed of a benzene structure with a mono-hydroxyl substitute cannot react with MG. Among benzenediols and di-hydroxyl benzoic acids, only hydroquinone reacted with MG and showed a 13% decrease in MG. Nevertheless, high reactivity was shown for 3 benzenetriols. The percentages of MG remaining were 45%, 51%, and 36% for pyrogallol, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene, respectively. When a carboxyl group is added to the benzenetriols, steric hindrance and carbon electron charges on benzene ring are the influential factors in reactivity. Using computational chemistry calculations, a carbon electron charge of -0.24 was the minimum value for high reactivity.