Mouse Transcriptome. Deficiency of Caspase-1 Attenuates HIV-1-Associated Atherogenesis in Mice.

This study delves into the impact of HIV infection within arterial plaque, focusing on its role in triggering inflammation and immune activation via the NLRP3/caspase-1 inflammasome pathway. Previous research had linked caspase-1 activation in myeloid cells to HIV-associated atherosclerosis in both mice and HIV-infected individuals. To investigate further, the researchers utilized caspase-1 deficient mice bred with HIV-1 transgenic mice on an atherogenic ApoE deficient background, creating global caspase-1 deficient mice. Control groups consisted of caspase-1 sufficient mice.Furthermore, chimeric hematopoietic cell-deficient mice were generated by transplanting bone marrow cells from either caspase-1 deficient or caspase-1 sufficient mice into irradiated ApoE deficient mice. The study's findings revealed that global caspase-1 knockout reduced plaque deposition in the thoracic aorta, lowered serum IL-18 levels, and decreased ex vivo foam cell formation. Hematopoietic cell deficiency of caspase-1 led to reduced atherosclerotic plaque burden throughout the aorta and aortic root, accompanied by decreased macrophage infiltration. Transcriptomic analyses of peripheral mononuclear cells and splenocytes indicated that caspase-1 deficiency inhibited genes related to the caspase-1 pathway. These results underscore the crucial role of caspase-1 in chronic HIV infection and emphasize its significance in HIV-associated atherosclerosis, shedding light on the implications of this pathway and peripheral immune activation in this condition.