Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

Table 2 Potential studies to elucidate sinusoidal pressure-mediated mechanisms of fibrosis

Potential studies to validate SPH
1. Matrix-modulating effects of pressure-lowering or modulating drugs.
2. Physical aspects of pressure formation in biological tissues including the role of cardiac pulse wave energy and its mechanic absorption by fat.
3. Effect of water metabolism, water channels (aquaporins), electrolyte transporters and other transporters and osmotic pressure on matrix formation.
4. Role of pressure-mediated biomechanic signaling for matrix formation including genetics, proteomics and metabolomics.
5. Role of ECM, cellular and inter-cellular junctions on pressure-mediated matrix formation.
6. Role of SP on gap junctions and matrix formation[78].
7. Role of vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids on SP and fibrosis[79].
8. Role of vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin and endothelin-1 on SP and fibrosis[80,81].
9. Optimization of pressure sensors e.g., for the liver sinus including the development of molecular stretch force measuring sensors[4].
10. Association of pressure, tissue/cellular stiffness and matrix formation at various organizational levels (cell, organ and whole organism).
11. Interplay of organ systems involved in water and pressure regulation (e.g., heart, brain, kidney and liver) for pressure regulation and matrix development.
12. Role of liver size and globularization of liver in various species in order to better sustain stretch forces of SP elevation.
13. Mechanisms and modulation of vessel and shunt formation in the liver.

ECM: Extracellular matrix; SP: Sinusoidal pressure; SPH: Sinusoidal pressure hypothesis.