Cardiovascular Research

Cardiovascular proteases

The cardiovascular system consists of the heart and blood vessels: arteries, veins, and capillaries. Proteases are vital to the regulation of its normal physiological state, but abnormal cardiovascular protease activities may lead to pathological processes such as atherosclerosis, altered blood coagulation, and hypertension.

Certain matrix metalloproteinases (MMPs), calpain, cathepsins and caspases are involved in cardiac remodeling associated with heart disease or damage. Low MMP ADAMTS-13 activity is associated with ischemic stroke. Renin, an aspartyl protease is involved in the activation of the renin–angiotensin system, which when overactive leads to hypertension. Plasmin activity necessary for dissolving blood clots, instead results in the formation of blood clots when its activity is disrupted.

Therefore, many cardiovascular associated proteases such as Thrombin, Factor Xa, and those previously mentioned can be potential therapeutic targets for drug discover.

FRET substrates

FRET occurs between a peptide tagged to a donor and an acceptor when placed within 10-100Å of each other resulting in the donor’s excitation fluorescence to be quenched by the acceptor. Enzymatic hydrolysis of the peptide results in recovery of the donor fluorescence following spatial separation of the donor and acceptor upon energy transfer.

Fluorogenic substrates

These substrates do not require a quencher and contain a C-terminal dye that does not fluoresce until it is cleaved from the peptide (fluorescent form of dye is released).