Nature knows how to make the best out of its tools, since it often re-cycles some good inventions from one species to another by introducing slight modifications. Something similar happened with proteins from the so-called Pentraxin family, already known for their role as markers of cardiovascular outcomes in humans, and recently proven to exert a protective function on the murine heart during experimental Acute Myocardial Infarction (AMI).

A team of Italian scientists - including EVGN pharmacologist Roberto Latini, from the Istituto di Ricerche Farmacologiche Mario Negri in Milan (Italy) – showed the positive role on the cardiac muscle of a specific Pentraxin called Prototypic Long Pentraxin (PTX3), which is rapidly produced when early inflammatory signals alert the organism. In particular, the investigation came to conclude that PTX3 plays a regulatory role on tissue damage when the heart suffers from oxygen scarcity (ischemia), suggesting its possible therapeutic use in ways still to be clarified. The discovery was published by the journal Circulation.

Proteins are grouped in families, according to function similarities or conservation degree among species during evolution. A well conserved  family is the Pentraxins family that hosts two interesting elements called short C-reactive protein (CRP) and long Pentraxin (PTX3). “We knew from previous works – explains Roberto Latini – that the presence of CRP indicates a higher risk of cardiovascular events, and that this protein somehow boost the tissue damage. We also knew that PTX3 is quickly released at the onset of inflammation, in response to early signals. Besides, it is present in human atherosclerotic lesions and its concentration peaks 7 hours after the first symptoms of AMI. However, we couldn’t tell whether it plays a direct pathogenetic role in Acute Myocardial Infarction. So we decided to investigate this issue using a mouse model genetically made unable to produce PTX3 (ptx-3 or knockout deficient) in the Laboratory of Immunology headed by Alberto Mantovani (Istituto Clinico Humanitas, Rozzano, Milano). This choice made sense because human and mouse proteins share part of their gene sequence, gene organization and mechanisms of regulation and function, which, on the contrary, is different between mouse and man for CRP. Hence, we expected to record in mice phenomena and behaviour that are similar to those we observe in humans”.

To begin with, the scientists induced an ischemic event in a group of mice, then monitored the concentration of ptx3 mRNA at different time points. mRNA molecules are indicative of the protein production: in general, the more mRNA the more protein is going to be synthesized. “There was a clear cut increase in ptx3 mRNA levels – says Latini – as these molecules peaked 4 hours after the damage and reached a plateau at 16 hours. Tissues other than the heart were not involved in this phenomenon”. This observation has its own importance, since a similar reaction can be recorded also in humans, at the very beginning of ischemic disorders.

Then, the team asked what could possibly be the functional role of PTX3. To find the answer the scientists repeatedly measured the infarct size and degree of reperfusion of the myocardium previously made ischemic, thus mimicking an AMI in man with early induced reperfusion. “We observed that when ptx3 is absent, as in the case of PTX3 ko mice, the cardiac tissue made ischemic and hen reperfused has a long and difficult recovery, as it is unable to re-grow a sufficient amount of capillaries and experiences a marked apoptosis, the cellular suicide that takes place when there is nothing more to do… Even more interesting is a significant impairment of spontaneous reperfusion upon surgical restoration of the blood flow in the absence of PTX3”.

Taken together, these observations point to a direct and beneficial role of the Prototypic Long Pentraxin (PTX3). “We need to understand a number of issues before thinking of applying PTX3 in human ischemic heart disorders” points out Latini. “But evidence provided by our study and more hopefully to come rises hope that this protein, or its modulation, could one day lead to a new generation of cardioprotectors”.

Full paper is available: Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction, Monica Salio et al., Circulation. 2008;117:1055-1064.