Yin Tintut - Academia.edu (original) (raw)

Papers by Yin Tintut

Biomolecules

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is n... more Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically impo...

Journal of Cellular Biochemistry

JCI insight, Jan 23, 2018

The ability to image tissue morphogenesis in real-time and in 3-dimensions (3-D) remains an optic... more The ability to image tissue morphogenesis in real-time and in 3-dimensions (3-D) remains an optical challenge. The advent of light-sheet fluorescence microscopy (LSFM) has advanced developmental biology and tissue regeneration research. In this review, we introduce a LSFM system in which the illumination lens reshapes a thin light-sheet to rapidly scan across a sample of interest while the detection lens orthogonally collects the imaging data. This multiscale strategy provides deep-tissue penetration, high-spatiotemporal resolution, and minimal photobleaching and phototoxicity, allowing in vivo visualization of a variety of tissues and processes, ranging from developing hearts in live zebrafish embryos to ex vivo interrogation of the microarchitecture of optically cleared neonatal hearts. Here, we highlight multiple applications of LSFM and discuss several studies that have allowed better characterization of developmental and pathological processes in multiple models and tissues. Th...

American journal of physiology. Heart and circulatory physiology, Jun 16, 2018

Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent mann... more Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit onset of aortic calcification. Whether teriparatide affects progression of pre-existing aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over one year to induce aortic calcification, treated for 4.5 weeks with daily injections of control vehicle (PBS), teriparatide 40 µg/kg (PTH40) or 400 µg/kg (PTH400), and assayed for aortic calcification by micro-computed tomography (microCT) before and after treatment. In a follow-up cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400, and assayed for aortic calcification by serial microCT and micro-positron emission tomography (microPET). In both cohorts, aortic calcification detected by microCT progressed similarly in all gr...

Circulation research, Jan 14, 2017

JCI insight, Nov 3, 2016

Emerging evidence indicates that upregulation of the ER stress-induced pro-osteogenic transcripti... more Emerging evidence indicates that upregulation of the ER stress-induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell-specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 play...

Heart (British Cardiac Society), Jan 12, 2016

Calcific diseases of the cardiovascular system, such as atherosclerotic calcification and calcifi... more Calcific diseases of the cardiovascular system, such as atherosclerotic calcification and calcific aortic valve disease, are widespread and clinically significant, causing substantial morbidity and mortality. Vascular cells, like bone cells, interact with their matrix substrate through molecular signals, and through biomechanical signals, such as traction forces transmitted from cytoskeleton to matrix. The interaction of contractile vascular cells with their matrix may be one of the most important factors controlling pathological mineralisation of the artery wall and cardiac valves. In many respects, the matricrine and matrix mechanical changes in calcific vasculopathy and valvulopathy resemble those occurring in embryonic bone development and normal bone mineralisation. The matrix proteins provide a microenvironment for propagation of crystal growth and provide mechanical cues to the cells that direct differentiation. Small contractions of the cytoskeleton may tug on integrin links...

Circulation Research, 2016

Trends in cardiovascular medicine, Jan 7, 2016

Atheroscler Suppl, 2003

Workshop 270 4WS26 ABC Transporters and Related Disorders is significantly impaired in klotho mic... more Workshop 270 4WS26 ABC Transporters and Related Disorders is significantly impaired in klotho mice and that urinary excretion of nitric oxide metabolites were significantly reduced in klotho mice. We have also found that superoxide production is increased in klotho mice. The expression of klotho mRNA in the kidney was significantly reduced in Dahl-S rats fed high salt (8% NaCl) diet as compared to those fed low salt (0.3% NaCl) diet (n=7). The klotho gene delivery once a week for 3 weeks induced klotho mRNA expression at the injection site. Hydroethidine, an oxidative fluorescent dye, was used to evaluate the levels of superoxide in situ. Intramuscular induction of the klotho gene decreased in superoxide production in the aorta, resulting in restoration of endothelial dysfunction from 43±6% to 61±9% of control rats (n=6, p<0.05). At the same time, systolic blood pressure was reduced from 262±11 mmHg to 234±6 mmHg (p<0.05). Furthermore, klotho gene delivery improved perivascular fibrosis from 0.31±0.02 to 0.11±0.01 mm 2 and reduced albuminuria from 655±220 to 96±24 mg/day (n=8, p<0.05). Our study indicates that intramusclar delivery of the klotho gene reduces oxidative stress and protects the vascular endothelium in Dahl-S rats. We suggest that induction of the klotho gene expression associated with the improvement of the endothelial function may be a potential novel therapeutic strategy for atherosclerosis.

Circulation, Nov 22, 2011

Free Radical Biology and Medicine, Mar 1, 2008

Biochemical and Biophysical Research Communications, 2008

Journal of Biological Chemistry, Jan 7, 1994

Functional Roles for the Glutamines within the Glutamine-rich Region of the Transcription Factor d4*

Journal of Bacteriology, 1995

Journal of Biological Chemistry

ABSTRACT

2012 IEEE 25th International Conference on Micro Electro Mechanical Systems (MEMS), 2012

ABSTRACT Regenerative medicine aims at cell-based therapy to rebuild the non-regenerative tissue.... more ABSTRACT Regenerative medicine aims at cell-based therapy to rebuild the non-regenerative tissue. To mimic the tissue development, supportive scaffolds have been intensively studied to allow cell attachment, migration, and to control delivery of essential factors. However, tissue is characterized by self-organization, which can limit the attempts to directly control the tissue development. Previously we applied local substrate discontinuity to cultured vascular stem cells (VSCs), which spontaneously aggregate into periodic multicellular patterns resembling normal tissue architectures [1], and showed that the substrate interface can led to change of pattern morphology via their inherent self-organization [2]. In the present study, we study the effects of 1) geometrical interface (micromachined surface geometrical step), 2) chemical interface (substrate discontinuity), and 3) cellular interface (stepwise cell distributions) to the development of global pattern formations. The findings suggest that cells sense the local stimuli and unfold it into multicellular structures, providing a new way for cell-based engineering of tissue architecture.

Arteriosclerosis Thrombosis and Vascular Biology