These last data suggest that the protective effect against chronic hypoxic PH may be related to alterations in the PDGFb and FGF2 pathways. Indeed, previous studies Norketamine hydrochloride showed that both growth factors played a key role in human and experimental PAH. The production of these growth factors or their receptors is increased in human PAH. Furthermore, inhibiting PDGFb or FGF2 synthesis using SiRNA or receptor antagonists protects and/or reverses PAH in experimental models. Our study establishes a key role for the TGF-b/ALK1/ENG signaling pathway in PAH and suggests that TGF-b may act upstream to pathways that are crucial in PAH in both humans and rodents, such as the Endothelin1, PDGFb, and FGF2 pathways. Common carotid intima media thickness, ankle brachial pressure index and whole body magnetic resonance angiography are all markers of atherosclerosis. Common carotid intima media thickness is a measure of early atherosclerosis and vascular remodelling which correlates highly with standard cardiovascular risk factors. This has been acknowledged by the FDA who have approved it as a marker of atherosclerosis. A reduction of CIMT thickness to lipid lowering agents has also been shown. These factors have led to the conclusion that it meets the criteria as a surrogate for CV disease endpoints, and can therefore be used as a primary outcome in clinical trials to allow for more rapid assessment and development of more effective treatments at lower cost. However its success in ML SA1 predicting risk of future cardiovascular events has been mixed with a recent meta-analysis showing it to add little benefit over the Framingham risk score in predicting future cardiovascular events. Additionally while some studies have shown good response of CIMT with statins, the ENHANCE trial showed a rise in CIMT with statins and ezetemide despite improved biochemical markers. The ankle brachial pressure index has primarily been used for the diagnosis and follow-up of lower extremity arterial disease, and has been shown to correlate with future cardiovascular events in groups with and without established peripheral arterial disease. Thus this has been suggested as a surrogate marker for systemic atherosclerosis. Whole body contrast-enhanced magnetic resonance angiography provides visualisation of the arterial tree from the skull vertex to the pedal arteries following the intravenous injection of a gadolinium based contrast agent. It can be used to quantify atheroma burden by scoring and summating the extent of stenosis in the arterial territories of the entire body.