We have shown that angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle cells is dependent on the balance between proliferatlve and antlproliferative growth factors, specifically basic fibroblast growth factor and transforming growth factor-/31 (TGF-01), respectively. We now present evidence, based on two phenotypically distinct cell cultures, that the ability to secrete the biologically active form of TGF-/31 is central to the growth response to Ang II. Two separate cultures were examined, one in which Ang II induces hypertrophy and the other in which Ang II induces hyperplasia. Ang II induces the expression of basic fibroblast growth factor twofold to fivefold in both cultures. Furthermore, both cultures express TGF-/J1. In the culture that responds with hypertrophy, Ang II induces the expression of the active form of TGF-/31 twofold to threefold. However, in the culture that responds with hyperplasia, no active TGF-/J1 was detected either at baseline or after Ang II exposure. Interestingly, all the TGF-01 present was in the inactive, latent form. In the culture that responded with hyperplasia, Ang II induced a fourfold to fivefold increase in DNA synthesis. This increase could be abolished by the addition of active TGF-01. Thus in these two cultures the ability to activate TGF-01 dictates the cellular response to Ang II. These results support our hypothesis that a balance of proliferative and antiproliferative autocrine signals mediates the growth control of vascular smooth muscle cells. 1 For example, hypertension results in vascular hypertrophy that in large conduit vessels, is due primarily to cellular hypertrophy, 2 whereas in resistance arteries hyperplasia predominates.3 In atherosclerosis, vascular smooth muscle proliferation within the intima is a major cause of plaque formation.1 Moreover, the vascular response to injury after mechanical trauma such as balloon angioplasty 4 also involves smooth muscle proliferation. The understanding of the mechanisms behind abnormal, uncontrolled proliferation is central to attempts to inhibit or control lesion formation.Among the factors responsible for the regulation of vascular smooth muscle growth, vasoactive substances play a major role. Angiotensin II (Ang II) has been used as a paradigm for these studies. In vivo, angiotensin converting enzyme (ACE) inhibitors attenuate the development of hypertension-induced vascular hypertro-
Time-resolved resonant inelastic X-ray scattering (RIXS) is one of the developing techniques enabled by the advent of X-ray free electron laser (FEL). It is important to evaluate how the FEL jitter, which is inherent in the self-amplified spontaneous emission process, influences the RIXS measurement. Here, we use a microchannel plate (MCP) based Timepix soft X-ray detector to conduct a time-resolved RIXS measurement at the Ti L3-edge on a charge-density-wave material TiSe2. The fast parallel Timepix readout and single photon sensitivity enable pulse-by-pulse data acquisition and analysis. Due to the FEL jitter, low detection efficiency of spectrometer, and low quantum yield of RIXS process, we find that less than 2% of the X-ray FEL pulses produce signals, preventing acquiring sufficient data statistics while maintaining temporal and energy resolution in this measurement. These limitations can be mitigated by using future X-ray FELs with high repetition rates, approaching MHz such as the European XFEL in Germany and LCLS-II in the USA, as well as by utilizing advanced detectors, such as the prototype used in this study.
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