Pathogenesis and Treatment Perspectives of Chronic Graft Rejection (CVR)

Abstract

Chronic rejection is a major threat towards the long-term function and survival of transplanted hearts and kidneys. It is characterized by a proliferative remodelling of the graft vessels along with structural changes of the parenchyma and gradual deterioration of graft function. The pathogenesis is complex and multifactorial. Since grafts with chronic rejection are also subjected to a more or less intense invasion of immunoreactive cells, an important primary objective is to optimize the immunosuppressive treatment. There is no established means of prevention or treatment of chronic rejection. Pharmacological agents interfering with prostaglandin metabolism have been tried most frequently and preliminary results are also available from the use of polyunsaturated fatty acids of the omega-3 series and of heparin derivatives. Based on experimental studies the somatostatin analogue angiopeptin seems very promising today. There will certainly be an increased interest in the use of lipid-reducing agents in the future as well as antioxidant agents acting against the effects of reactive oxygen radicals and oxidative modification of LDL fractions. A strong novel candidate is carvedilol, exerting both antihypertensive, antioxidant and antiproliferative properties.

Accelerated atherosclerosis in the transplant recipient: role of hypertension

“…5,6,14 The alloreaction participates in the development of CVR mainly through activated monocytes and macrophages. These cells have the ability to synthesise and secrete both cytokines and more specifically growth factors, which act upon smooth muscle cells and fibroblasts by stimulating proliferation and synthesis of connective tissue proteins.…”

“…This is also called chronic rejection (CVR) or chronic transplant dysfunction, which is considered to be one of the leading causes of long-term failure of transplanted hearts and kidneys. [5][6][7][8] It has been estimated from various investigations that there is a 3-4% annual loss of transplanted kidneys due to chronic rejection Ͼ1 year post-transplantation. In …”

Inhibition of Myointimal Proliferation by Octreotide in Canine Vein Interposition Grafts

“…The main component of this thickening was a result of smooth muscle cells containing large amounts of synthetic organelles, characteristic of the secretory phenotype of smooth muscle cells. Smooth muscle cells were observed migrating through the internal elastic lamina [3][4][5].…”

“…Octreotide is also an agent inhibiting the proliferation of cells. However, it has a short half-life [3][4][5].…”

“…The effect of octreotide was also studied in the animal model of arterialized venous interposition grafts. Later, the inhibitory effects on myointimal proliferation of octreotide and other analogues were studied in animal models of vascular injury [1,[3][4][5].…”