Mitochondrial protein ALDH4A1 is identified as a potential marker for the diagnosis and treatment target for cardiovascular disease (CVD), as per a study at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), published in the journal Nature.
Cardiovascular disease is the leading cause of death in the world, with heart attack or stroke being the most common. This is commonly precipitated by thrombosis - clinical manifestation of atherosclerosis (a chronic inflammatory disease that produces plaques). Atherosclerosis develops over many years without causing symptoms,in the blood vessel wall, and is composed of cell debris, fats, and fibrous material.
Study leader Dr. Almudena Ramiro, of the CNIC, explained that "we know that atherosclerosis includes an immunological component and that the innate and adaptive immune systems are both involved in the origin and progression of this disease." However, the subject requires further evidence.
The study explored the mitochondrial protein - ALDH4A1, an autoantigen, involvement in antibody response of atherosclerosis via a mouse lacking the low-density lipoprotein receptor (LDLR-/-), fed a high-fat diet. The levels of ALDH4A1 accumulate in plaques and its plasma concentration is elevated in the atherosclerosis-prone. "ALDH4A1 is recognized by the protective antibodies produced during atherosclerosis, making it a possible therapeutic target or diagnostic marker for this disease," Ramiro said.
Autoantigens are a type of protein molecules that are produced by the body and recognized as foreign substance to trigger an immune response.
Specifically, the antibody A12 was able to recognize plaques not only in the atherosclerosis-prone mice but also in samples from patients with atherosclerosis in the carotid arteries. "Proteomics analysis showed that A12 specifically recognized a mitochondrial protein called aldehyde dehydrogenase 4 family, member A1 (ALDH4A1), identifying this protein as an autoantigen in the context of atherosclerosis," said first author Cristina Lorenzo.
Thus, the study highlights the role of ALDH4A1 as a new biomarker and A12 as a therapeutic agent for treating atherosclerosis to prevent further worsening of cardiovascular diseases.