Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

The pathogenesis of atherosclerosis: a perspective for the 1990s

https://www.cell.com/cell/pdf/S0092-8674(00)80949-6.pdf

Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

IS097 Chronic treatment with endothelin inhibitor greatly improves survival in hamsters with heart failure due to dilated cardiomyopathy : increased expression of endothelin-1 in failing heart

Mechanism of regulation of the ΕΤβ mRNA expression in primary cultured astrocytes

Plasma concentration of and pulmonary vascular response to endothelin-1 in rats with pulmonary hypertension.

CGRP in the regulation of cardiac function

Elucidation With the Protease α-Chymotrypsin of the Inhibitory Modulating Action of Endogenous Neuropeptide Y Over Sympathetic Neurotransmission in Rat Vas Deferens

Katsutoshi Goto

Papers

IS097 Chronic treatment with endothelin inhibitor greatly improves survival in hamsters with heart failure due to dilated cardiomyopathy : increased expression of endothelin-1 in failing heart

Mechanism of regulation of the ΕΤβ mRNA expression in primary cultured astrocytes

Plasma concentration of and pulmonary vascular response to endothelin-1 in rats with pulmonary hypertension.

CGRP in the regulation of cardiac function

Elucidation With the Protease α-Chymotrypsin of the Inhibitory Modulating Action of Endogenous Neuropeptide Y Over Sympathetic Neurotransmission in Rat Vas Deferens