A 2kg human liver contains about 109 1mm long in-parallel sinusoids within 106 lobules and perfused by 2 litres blood/minute, forming an endothelial-hepatocyte area approximating that of a tennis-court. The porosity of its fenestrated sinusoidal endothelial cells (LSECs) regulates sieving of lipoproteins between the blood and hepatocytes.
Dietary triglycerides increase sizes of chylomicrons, while a decreased LSEC porosity (from fewer or smaller fenestrae) is often seen during experimental atherosclerosis. Chylomicrons transporting dietary lipids in the blood shed fatty acids to organs (for fuel or storage) to become smaller cholesterol-rich remnants. Remnants then traverse LSEC fenestrae for uptake by hepatocytes to inhibit HMG CoA Reductase, thus balancing dietary and liver-synthesised cholesterol.
Our poster was first exhibited at the European Atherosclerosis Society, Gothenburg (2012) and at the International Atherosclerosis Society, St Petersburg (2016). I chaired the “Anitschkow Legacy” session celebrating his discovery (1913) that cholesterol-fed rabbits develop atherosclerosis. At a much earlier IAS meeting in Tokyo (1976) we first attributed the rabbits’ cholesterol sensitivity to low porosity LSECS. This finding explained many familial and lifestyle factors associated with atherosclerosis.
After seven years absence from ISCHS, we again stress the correlation between addictive lifestyles, involving nicotine and alcoholism, with decreased LSEC porosity and atherosclerosis. LSEC ultrafiltration of other nanoparticles may also influence multiple diseases such as diabetes. LSEC porosity maybe altered by portal pressure, sleep-apnoea, exercise, arsenic, microbiome and ageing.
We answer YES to our poster’s question. With our updated data we hope Hans and Karl Popper might agree. However we crave a simple clinical test for LSEC porosity.
