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Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly (lactic acid‐co‐glycolic acid)‐block‐poly (ethylene glycol)‐block‐poly (lactic acid‐co‐glycolic acid) gel (PLGA‐PEG‐PLGA) system encapsulating tanshinone IIA‐loaded reactive oxygen species‐sensitive microspheres (Gel−MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species‐triggered release properties in a high‐reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local anti‐pyroptotic and anti‐inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone IIA. Therefore, this novel, precision‐guided intra‐tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post‐infarct heart. [ABSTRACT FROM AUTHOR]

Elastin is a major component of conduit arteries and a key determinant of vascular viscoelastic properties. Aberrant organization of elastic lamellae has been reported in resistance vessels from spontaneously hypertensive rats (SHR) before the development of hypertension. Hence, we have characterized the content and organization of elastic lamellae in conduit vessels of neonatal SHR in detail, comparing the carotid arteries from 1-wk-old SHR with those from Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats. The general structure and mechanics were studied by pressure myography, and the internal elastic lamina organization was determined by confocal microscopy. Cyanide bromide-insoluble elastin scaffolds were also prepared from l-mo-old SHR and WKY aortas to assess their weight, amino acid composition, three-dimensional lamellar organization, and mechanical characteristics. Carotid arteries from 1-wk-old SHR exhibited narrower lumen and greater intrinsic stiffness than those from their WKY and SD counterparts. These aberrations were associated with heightened elastin content and with a striking reduction in the size of the fenestrae present in the elastic lamellae. The elastin scaffolds isolated from SHR aortas also exhibited increased relative weight and stiffness, as well as the presence of peculiar trabeculae inside the fenestra that reduced their size. We suggest that the excessive and aberrant elastin deposited in SHR vessels during perinatal development alters their mechanical properties. Such abnormalities are likely to compromise vessel expansion during a critical period of growth and, at later stages, they could compromise hemodynamic function and participate in the development of systemic hypertension. remodeling; hypertension; elastic lamellae; fenestrae; spontaneously hypertensive rats

Elastic fibers play a key role in the structure and function of numerous organs that require elasticity. Elastogenesis is a complex process in which cells first produce a microfibrillar scaffold, composed of numerous structural proteins, upon which tropoelastin assembles to be cross-linked into polymeric elastin. Recently, it was demonstrated that low concentrations of free iron upregulate elastin gene expression in cultured fibroblasts. The present studies were conducted to assess whether low-iron diets would affect the deposition of elastic fibers in an in vivo model. One-day-old chicks were fed semipurified diets containing 1.3 (low), 12 (moderate), and 24 (control) mg/kg of iron. After 3 wk, chicks in the low-iron group were underweight and anemic. Their aortas were smaller with significantly thinner walls than control chicks, yet elastin or collagen content did not decrease relative to total protein. They also demonstrated a significantly lower stress-strain resistance than the controls. Electron microscopy demonstrated that aortic and lung smooth muscle cells were vacuolated and surrounded by loose extracellular matrix and disorganized elastic lamellae with diffuse and fragmented networks of elastic fibers and microfibrils. Immunohistology demonstrated that fibrillin-3 (FBN3) was disorganized and markedly reduced in amount in aortas of the low-iron chicks. Elastin messenger RNA levels were not downregulated in the tissues from the low-iron-fed chicks; however, there was a significant reduction in expression of the FBN1 and FBN3 genes compared with control chicks. The studies indicate that iron deficiency had a pronounced negative effect on elastic fiber development and suggests that fibrillin may have an important role in this pathology.

Author(s): Tomoyuki Nakamura [1]; Pilar Ruiz Lozano [1]; Yasuhiro Ikeda [1]; Yoshitaka Iwanaga [1, 2]; Aleksander Hinek [3]; Susumu Minamisawa [1]; Ching-Feng Cheng [1]; Kazuhiro Kobuke [4]; Nancy Dalton [1]; [...]

Functional regions in the alpha and beta subunits of beta-hexosaminidase were localized by cellular expression of alpha/beta fusion proteins joined at adjacently aligned residues. Findings indicated that the region responsible for the capability of the alpha subunit to bind negatively charged substrates is found within residues alpha-132 to 283. The remaining carboxy-terminal section from the beta chain beta-316 to 556, was enough to enable this chimera to hydrolyze G(sub M2) ganglioside with 10% the specific activity of heterodimeric hexosaminidase A.