Opposite Role of Pro‐Inflammatory Alleles in Acute Myocardial Infarction and Longevity

Abstract

The major trait characterizing offspring in centenarians is a reduction in the prevalence of cardiovascular disease. Because a pro-inflammatory genotype seems to contribute significantly to the risk of coronary heart disease, alleles associated with disease susceptibility would not be included in the genetic background favoring longevity, as suggested by our previous studies on inflammatory cytokines. To confirm whether genotypes of inflammatory molecules play an opposite role in atherosclerosis and longevity, we are studying the role of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial infarction and longevity. The results support the hypothesis that the genetic background favoring cardiovascular diseases is detrimental to longevity. In addition, they suggest that the centenarian genetic background may be useful for investigating genetic key components of age-associated diseases that are characterized by a multifactorial etiology.

Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity

“…So, genetic background promoting pro-inflammatory responses may play an opposite role in CVD and longevity. 8 In agreement with our hypothesis the results show that the role of CCR5∆32 variant confers AMI resistance and promotes longevity in Sicilians.…”

“…We also analyzed their distribution in centenarians, since our previous studies have demonstrated that alleles associated with AMI susceptibility are not included in the genetic background favoring longevity. 8 We enrolled 133 young subjects (<45 years) selected among AMI patients admitted to the Intensive Coronary Therapy Unit of Palermo University Hospital. Diagnosis was based on identification of electrocardiograph and serum enzyme activity changes confirmed by echocardiography and coronary angiography.…”

“…Since centenarian offspring seem to have a significant reduction in CVD prevalence, 8 we performed centenarian genetic studies to clarify the role of key genetic components influencing AMI. We have demonstrated in previous studies that alleles associated to CHD susceptibility are not included in the genetic background favoring longevity.…”

CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5

“…Serum IFN-ß levels have previously been shown to be significantly elevated in patients who cleared the virus spontaneously in comparison with patients having virus persistence [9, 19]. Since the presence of one minor allele has already been associated with reduced receptor function in binding its ligands MIP-1α, MIP-1β, RANTES, and MCP-2 [32], a deletion in the CCR5 gene implies an involvement of immune system components as shown for impaired macrophage and leukocyte infiltration [33, 34], systemic inflammation [12], and the evolutionary pro-inflammatory response [35]. CCR5 is not the unique receptor for its natural ligands, which also use CCR1 [36, 37].…”

Connexin37 1019 gene polymorphism in myocardial infarction patients and centenarians

“…Individuals with exceptional longevity possess indeed genetic factors that modulate ageing processes and, in particular, are protective versus cardiovascular diseases. So, pro/anti-inflammatory alleles have a role in determining susceptibility or resistance to immune-inflammatory diseases, including atherosclerosis, and reciprocally in determining or not the possibility to reach the extreme limit of life [4,5]. It is intriguing that in a mouse model of atherosclerosis, the mouse Cx37 protein was shown to be atheroprotective by properly regulating leukocyte recruitment, namely one of the first inflammatory steps in atherosclerotic process [6].…”