Regulation of smooth muscle cell accumulation in diabetes-accelerated atherosclerosis

Diabetes leads to accelerated formation/ progression of lesions of atherosclerosis. Cardiovascular disease thus develops earlier in people with type 1 or type 2 diabetes compared to people without diabetes, and cardiovascular (macrovascular) disease is the major cause of death in adults with diabetes. The molecular and cellular mechanisms leading to diabetes-accelerated atherosclerosis are not well understood. The arterial smooth muscle cell (SMC), one of the three or four principal cell types in atherosclerosis, has been extensively studied over the years. Proliferation and accumulation of SMCs are believed to play important roles in the progression of macrophage-rich lesions to fibroatheromas. Further progression of these atheromas into complicated vulnerable lesions that are likely to cause the acute clinical symptoms of atherosclerosis (myocardial infarction and stroke) may involve cell death and loss of SMCs from the fibrous cap of the lesion. Recent animal studies have shown that diabetes causes a marked increase in SMC accumulation and proliferation in atheromas. Hyperglycemia, advanced glycation end-products, insulin and lipid abnormalities associated with the diabetic environment have been suggested to increase SMC accumulation. Indeed, it is becoming increasingly clear that macrovascular disease associated with diabetes is a multifactorial disease. We review the factors and mechanisms that may regulate SMC proliferation and accumulation in different stages of lesion progression in diabetes. We propose that lipid abnormalities associated with diabetes can act in combination with growth factors present in the diabetic environment to increase SMC accumulation and accelerate lesion progression

Insulin-like growth factor and growth hormone receptor in postpartum lactating beef cows Fator de crescimento semelhante à insulina e receptor do hormônio do crescimento no pós-parto de vacas de corte

The objective of this study was to evaluate the plasma concentrations of insulin-like growth factor-I (IGF-I), and the mRNA hepatic expression of IGF-I and of the growth hormone receptors GHR and GHR 1A, in postpartum beef cows. Four Angus and four crossbred (Angus x Nelore) postpartum suckled beef cows were used. Liver and blood samples were collected every 10 days, from calving to 40 days postpartum, for gene expression and for &#946;-hydroxybutyrate and IGF-I assays, respectively. Samples for progesterone assay were collected every other day, from day 10 to 40 postpartum. Three cows ovulated before 40 days postpartum. IGF-I concentration was higher in Angus x Nelore than in Angus cows. There was no difference in the expression of GHR, GHR 1A and IGF-I according to breed or ovulatory status. IGF-I concentrations were higher in crossbred cows, but have not changed according to postpartum ovulatory status. Moreover, changes in postpartum IGF-I concentrations are not associated with changes in liver GHR, GHR 1A and IGF-I mRNA expression in either breed.<br>O objetivo deste estudo foi avaliar as concentrações plasmáticas do fator de crescimento semelhante à insulina tipo I (IGF-I) e a expressão hepática de mRNA de IGF-I e dos receptores do hormônio de crescimento GHR e GHR 1A, no pós-parto de vacas de corte. Quatro vacas Angus e quatro mestiças (Angus x Nelore) lactantes foram usadas durante o período de pós-parto. As coletas de tecido hepático e de sangue foram realizadas a cada dez dias, do parto até 40 dias pós-parto, para a avaliação da expressão gênica, e análise de &#946;-hidroxibutirato e IGF-I, respectivamente. As amostras para análise de progesterona foram coletadas a cada dois dias, dos dez aos 40 dias pós-parto. Três vacas ovularam antes dos 40 dias pós-parto. A concentração de IGF-I foi maior em vacas Angus x Nelore do que em vacas Angus. Não houve diferença na expressão hepática de GHR, GHR 1A e IGF-I de acordo com a raça ou com a ovulação. As concentrações de IGF-I foram maiores em vacas cruzadas, e não mudaram com o status ovulatório pós-parto. Além disso, as mudanças observadas na concentração de IGF-I, durante o período pós-parto, não estão associadas a alterações na expressão hepática de mRNA de GHR, GHR 1A e IGF-I, em nenhuma das duas raças

The mechanisms of coronary restenosis: insights from experimental models

Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, ‘in-stent’ stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis